28 results on '"Yukiyoshi Ajisawa"'
Search Results
2. Effects of Selective β2 and β3-Adrenoceptor Agonists on Detrusor Hyperreflexia in Conscious Cerebral Infarcted Rats
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Kouichi Kaidoh, Hiroshi Miyata, Satoshi Akahane, Karl-Erik Andersson, Osamu Nishizawa, Yasuhiko Igawa, Yukiyoshi Ajisawa, Hiroo Takeda, and Yoshinobu Yamazaki
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Detrusor muscle ,Urinary bladder ,medicine.diagnostic_test ,business.industry ,Cerebral infarction ,Urology ,Urinary system ,Ischemia ,Cystometry ,medicine.disease ,medicine.anatomical_structure ,Anesthesia ,medicine.artery ,Middle cerebral artery ,medicine ,business ,Artery - Abstract
Purpose: We evaluated the effects of β-adrenoceptor agonists on detrusor hyperreflexia in cerebral infarcted rats.Materials and Methods: To produce cerebral infarction in Sprague-Dawley rats the left middle cerebral artery was occluded by introducing a monofilament nylon thread into the artery. In sham operated rats the same artery was exposed but not occluded. After these operations cystometric and cardiovascular experiments were performed with no anesthesia or restraint.Results: After the operation bladder capacity was significantly decreased and voiding pressure was significantly increased in cerebral infarcted but not in sham operated animals. The difference in cerebral infarcted and sham operated rats was significant for each parameter (p
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- 2002
3. RELAXANT EFFECTS OF ISOPROTERENOL AND SELECTIVE β3-ADRENOCEPTOR AGONISTS ON NORMAL, LOW COMPLIANT AND HYPERREFLEXIC HUMAN BLADDERS
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Karl-Erik Andersson, Yukiyoshi Ajisawa, Yoshinobu Yamazaki, Osamu Nishizawa, Kouichi Kaidoh, Hiroo Takeda, Takehisa Yoneyama, Yasuhiko Igawa, and Masuo Akahane
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Male ,Agonist ,medicine.medical_specialty ,medicine.drug_class ,Procaterol ,Muscle Relaxation ,Urology ,Urinary Bladder ,Stimulation ,In Vitro Techniques ,chemistry.chemical_compound ,Internal medicine ,medicine ,Humans ,Urinary Bladder, Neurogenic ,Forskolin ,Urinary bladder ,medicine.diagnostic_test ,business.industry ,Isoproterenol ,Cystometry ,Muscle, Smooth ,Adrenergic beta-Agonists ,Middle Aged ,Muscle relaxation ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Female ,Detrusor sphincter dyssynergia ,business ,medicine.drug - Abstract
We compared the relaxant effects of the stimulation of beta-adrenoceptors with isoproterenol and of drugs selective for beta-adrenoceptor subtypes in detrusor preparations from patients with normal and neurogenic bladder, respectively.We studied in vitro preparations of a cystometrically normal, low compliant and hyperreflexic bladder from 45, 26 and 7 patients, respectively.Isoproterenol relaxed concentration dependently and with the same potency as detrusor preparations obtained from normal and neurogenic bladders. In 37 normal detrusor, 25 low compliant and 7 hyperreflexic cases pD2 values were 6.36, 6. 25 and 6.38, respectively. Maximal relaxation did not differ significantly among the 3 groups (about 80% of 10-5 M. forskolin induced relaxation). Neither the beta1-/beta2-adrenoceptor agonist dobutamine nor the beta2-adrenoceptor agonist procaterol produced any significant relaxation of preparations from the 3 groups at a concentration of up to 10-5 M. At a concentration of 10-4 M. the preparations were relaxed but neither of these effects reached a maximum. BRL37344A and CL316243, selective beta3-adrenoceptor agonists and CGP-12177A (a selective beta3-adrenoceptor partial agonist and beta1-/beta2-adrenoceptor antagonist) relaxed detrusor preparations from the normal, low compliant and hyperreflexic groups when applied at concentrations greater than 10-6 M. For each agonist the pD2 value did not differ significantly among the 3 groups.beta-adrenoceptor stimulation is an effective way of relaxing the human detrusor and the effect is similar in normal and neurogenic bladders. A major portion of the relaxant effect of isoproterenol is mediated via beta3-adrenoceptor stimulation. Clinical trials may reveal whether this method is useful for treating bladder overactivity.
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- 2001
4. EXISTENCE OF A ??3-ADRENOCEPTOR AND ITS FUNCTIONAL ROLE IN THE HUMAN URETER
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YOUNG-CHOL PARK, YOSHITAKA TOMIYAMA, KOHICHI HAYAKAWA, MASUO AKAHANE, YUKIYOSHI AJISAWA, RYUICHIRO MIYATAKE, HIRO KIWAMOTO, TAKAHIDE SUGIYAMA, and TAKASHI KURITA
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Urology - Published
- 2000
5. EXISTENCE OF A β3-ADRENOCEPTOR AND ITS FUNCTIONAL ROLE IN THE HUMAN URETER
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Takahide Sugiyama, Masuo Akahane, Yukiyoshi Ajisawa, Yoshitaka Tomiyama, Kiwamoto H, Takashi Kurita, Kohichi Hayakawa, Young-Chol Park, and Ryuichiro Miyatake
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Agonist ,medicine.medical_specialty ,Messenger RNA ,business.industry ,Procaterol ,medicine.drug_class ,Urology ,Reverse transcription polymerase chain reaction ,Endocrinology ,Ureter ,medicine.anatomical_structure ,Internal medicine ,Isoprenaline ,Gene expression ,Medicine ,Dobutamine ,business ,medicine.drug - Abstract
Purpose: We tried to determine the β-adrenoceptor (AR) subtypes distributed in the human ureter and to clarify their functional role in ureteral relaxation.Materials and Methods: 1) Effects of β-AR agonists on either spontaneous or KCl-induced contractions of the human ureter and the antagonism by β-AR antagonists on isoprenaline (a non-selective β-AR agonist)-induced effects were evaluated in vitro. 2) Displacement by β-AR antagonists of [3H]-dihydroalprenolol binding to a membrane preparation derived from human ureteral smooth muscle was evaluated. 3) A reverse transcription polymerase chain reaction assay was performed to determine the expression of the mRNA for β1-, β2- and β3-ARs in human ureteral smooth muscle.Results: 1) Isoprenaline and procaterol (a β2-AR agonist) concentration-dependently suppressed both spontaneous and KCl-induced contractions of the human ureter. The β3-AR agonists, CGP-12177A and CL-316243, also suppressed these ureteral contractions, but dobutamine (a β1-AR agonist) had litt...
- Published
- 2000
6. Inhibitory Effects of Tranilast on the Proliferation and Functions of Human Pterygium-derived Fibroblasts
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Shinji Kikuchi, Kaori Araki-Inazawa, Hiroshi Miyata, Yuji Tsukamoto, Yoshinari Amano, Yukiyoshi Ajisawa, and Masayuki Isaji
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Contraction (grammar) ,Tranilast ,Pterygium ,Inhibitory postsynaptic potential ,Immunoenzyme Techniques ,Hemocytometer ,Anti-Allergic Agents ,medicine ,Humans ,ortho-Aminobenzoates ,Cells, Cultured ,Chemistry ,Chemotaxis ,Fibroblasts ,Molecular biology ,Actins ,eye diseases ,Collagen gel ,Ophthalmology ,Collagenase ,Immunohistochemistry ,Collagen ,sense organs ,Cell Division ,medicine.drug - Abstract
Purpose We studied the possibility that tranilast, an antiallergic and antiproliferative drug, may be beneficial for the treatment of pterygium. Methods Pterygium-derived cells were identified by immunohistochemical methods. Growth rate of pterygium-derived cells was determined by using a hemocytometer. Chemotaxis was determined in a microchemotaxis chamber. Pterygium-derived cells were cultured on floating collagen gel, and the contracted diameter was measured. Collagen synthesis by pterygium-derived cells was determined by the collagenase digestive method. Tranilast was added to the culture medium at final concentrations of 0, 12.5, 25, 50, and 100 microg/ml. Results Pterygium-derived cells were stained with anti-prolylhydroxylase and anti-alpha-smooth muscle actin, and identified as fibroblasts. Tranilast inhibited the proliferation and chemotaxis of pterygium-derived fibroblasts, and the collagen-gel contraction induced by these cells, but it exerted no inhibitory action on collagen synthesis by pterygium-derived fibroblasts. Conclusion Tranilast may be useful for suppressing the recurrence and, possibly, the development of pterygium.
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- 2000
7. Functional and molecular biological evidence for a possible β 3 -adrenoceptor in the human detrusor muscle
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Yoshinobu Yamazaki, Takehisa Yoneyama, Karl-Erik Andersson, Osamu Nishizawa, Yasuhiko Igawa, Hiroo Takeda, Kohichi Hayakawa, Yukiyoshi Ajisawa, and Masuo Akahane
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Pharmacology ,Detrusor muscle ,Beta-3 adrenergic receptor ,medicine.medical_specialty ,Forskolin ,Chemistry ,Antagonist ,Adrenergic ,musculoskeletal system ,chemistry.chemical_compound ,medicine.anatomical_structure ,Endocrinology ,Muscle relaxation ,Isoprenaline ,Internal medicine ,medicine ,Receptor ,medicine.drug - Abstract
The possible existence of a beta3-adrenergic receptor (beta3-AR) in the human detrusor muscle was investigated by in vitro functional studies and analysis of mRNA expression. Isoprenaline, noradrenaline and adrenaline each produced a concentration-dependent relaxation of the human detrusor. The rank order for their relaxing potencies was isoprenaline (pD2 6.37+/-0.07) > or = noradrenaline (pD2 6.07+/-0.12) > or = adrenaline (pD2 5.88 M) and its pKB value was 5.71+/-0.19. Moreover, SR58894A (10(-7) - 10(-5) M), a beta3-AR antagonist, caused a rightward shift of the concentration-relaxation curve for isoprenaline in a concentration-dependent manner. The pA2 value and slope obtained from Schild plots were 6.24+/-0.20 and 0.68+/-0.31. The beta1-, beta2- and beta3-AR mRNAs were all positively expressed in detrusor smooth muscle preparations in a reverse transcription polymerase chain reaction assay. In conclusion, the present results provide the first evidence for the existence of the beta3-AR subtype in the human detrusor. They also suggest that the relaxation induced by adrenergic stimulation of the human detrusor is mediated mainly through beta3-AR activation.
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- 1999
8. Tranilast: A New Application in the Cardiovascular Field as An Antiproliferative Drug
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Masayuki Isaji, Yukiyoshi Ajisawa, and Hiroshi Miyata
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Pharmacology ,Drug ,Pharmacokinetics ,business.industry ,In vivo ,media_common.quotation_subject ,Tranilast ,Medicine ,Cardiology and Cardiovascular Medicine ,business ,media_common ,medicine.drug - Published
- 1998
9. β-Adrenoceptor subtypes in the ureteral smooth muscle of rats, rabbits and dogs
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Yukiyoshi Ajisawa, Yoshitaka Tomiyama, Kazuhiko Shinagawa, Kohichi Hayakawa, Takashi Kurita, Masuo Akahane, and Young-Chol Park
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Male ,Agonist ,medicine.medical_specialty ,Procaterol ,medicine.drug_class ,Muscle Relaxation ,Adrenergic ,Rats, Sprague-Dawley ,Catecholamines ,Dogs ,Isoprenaline ,Internal medicine ,Receptors, Adrenergic, beta ,medicine ,Animals ,Pharmacology ,Lagomorpha ,biology ,Chemistry ,Antagonist ,Muscle, Smooth ,Adrenergic beta-Agonists ,biology.organism_classification ,Rats ,Endocrinology ,Bupranolol ,Female ,Dobutamine ,Rabbits ,Ureter ,medicine.drug - Abstract
We investigated the beta-adrenoceptor subtypes mediating ureteral relaxation in rats, rabbits and dogs. The relaxing effects of beta-adrenoceptor agonists were evaluated on KCl-induced ureteral contractions. The rank order of potency of the catecholamines tested was isoprenaline > noradrenaline > adrenaline in rat ureter; isoprenaline > adrenaline > noradrenaline in rabbit ureter; only isoprenaline was effective in canine tissues. The beta1-adrenoceptor agonist, dobutamine, produced relaxation of rat ureter. The beta2-adrenoceptor agonist, procaterol, produced more significant relaxation of rabbit ureter than did dobutamine. CL-316243 [(R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethylamino]propyl]-1,3-b enzodioxole-2,2-dicarboxylate] and CGP-12177A [(+/-)[4-[3[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-+ ++benzimidazol-2-one hydrochloride], beta3-adrenoceptor agonists, were more effective in relaxing canine ureter than were dobutamine and procaterol. Isoprenaline-induced relaxation was antagonized by a beta1-adrenoceptor antagonist, CGP-20712A [2-hydroxy-5(2-((2-hydroxy-3-(4-((1-methyl-4-trifluoromethyl)1H-imidazol e-2-yl)phenoxy)propyl)amino)ethoxy)-benzamide monomethane sulphonate], in rats and by a beta2-adrenoceptor antagonist, ICI-118,551 [(+/-)-1-[(2,3-dihydro-7-methyl- 1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride], in rabbits. The non-selective beta-adrenoceptor antagonist, bupranolol, antagonized isoprenaline-induced relaxation in all species tested. In conclusion, beta-adrenoceptor agonists may relax ureter by stimulating mainly beta1-adrenoceptors in rats, beta2-adrenoceptors in rabbits and mainly beta3-adrenoceptors in dogs.
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- 1998
10. Species differences in the distribution of β -adrenoceptor subtypes in bladder smooth muscle
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Yoshinobu Yamazaki, Osamu Nishizawa, Masuo Akahane, Hiroo Takeda, Yukiyoshi Ajisawa, and Yasuhiko Igawa
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Pharmacology ,Agonist ,Detrusor muscle ,medicine.medical_specialty ,Lagomorpha ,biology ,Chemistry ,medicine.drug_class ,Procaterol ,Antagonist ,biology.organism_classification ,Endocrinology ,medicine.anatomical_structure ,Internal medicine ,Isoprenaline ,Bupranolol ,medicine ,medicine.symptom ,medicine.drug ,Muscle contraction - Abstract
1. The beta-adrenoceptor (beta-AR) subtypes mediating relaxation of the rabbit, rat and canine detrusors were subjected to functional investigation using selective beta-AR agonists and antagonists. 2. In all three species, isoprenaline, noradrenaline and adrenaline each produced a concentration-dependent relaxation of the detrusor. The rank order for their relaxing potency was isoprenaline>adrenaline>noradrenaline in rabbits and rats, but isoprenaline>noradrenaline>adrenaline in dogs. 3. Dobutamine did not produce relaxation of the detrusors at concentrations that are selective for beta1-AR. The selective beta2-AR agonist, procaterol, had a more potent relaxing effect on rabbit and rat detrusors than on the canine detrusor. CGP-12177A, a selective beta3-AR agonist, was more effective in the rabbit than in the other two species. On the other hand, the relaxing effect of another beta3-AR agonist, CL316243, was more pronounced in dogs and rats than in rabbits. 4. CGP-20712A (10(-9) to 10(-7) M), a selective beta1-AR antagonist, caused a slight rightward shift of the concentration-relaxation response curve for isoprenaline in the canine detrusor (pA2 9.41), but not in the rabbit and rat detrusors. ICI-118,551, a selective beta2-AR antagonist, antagonized the isoprenaline-induced relaxation in rabbits (pA2 9.45) and rats (pA2 9.05), but not in dogs. Bupranolol, a non-selective beta-AR antagonist, caused a rightward shift of the concentration-relaxation curve for isoprenaline in the rabbit (pA2 9.32) and rat (pA2 8.98). However, higher concentrations (3 x 10(-8) to 10(-5) M) were needed to induce a rightward shift of the curve for isoprenaline in the dog (pA2 8.19) than in the other two species. 5. We have confirmed that the distribution of beta-AR subtypes in the detrusor muscle varies significantly from species to species and we provide here the first evidence of the presence of beta3-AR in the detrusor. It is suggested that the relaxation induced by adrenoceptor agonists in urinary bladder smooth muscle may be mediated mainly via beta2-AR in rabbits, via both beta2- and beta3-AR in rats, but mainly via beta3-AR in dogs.
- Published
- 1998
11. Comparison of in vitro and in vivo inhibitory effects of peptide and nonpeptide oxytocin antagonists on radioligand binding and uterine contractility of rats during pregnancy
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Mamoru Kobayashi, Masuo Akahane, Yukiyoshi Ajisawa, and Tatsuhiko Kawarabayashi
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endocrine system ,medicine.medical_specialty ,Uterus ,Neuropeptide ,In Vitro Techniques ,Peptide hormone ,Dinoprost ,Oxytocin ,Oxytocin Antagonist ,Uterine contraction ,Radioligand Assay ,Uterine Contraction ,Hormone Antagonists ,Pregnancy ,In vivo ,Internal medicine ,Animals ,Medicine ,Rats, Wistar ,business.industry ,Obstetrics and Gynecology ,Oxytocin receptor ,Rats ,medicine.anatomical_structure ,Endocrinology ,Receptors, Oxytocin ,Pregnancy, Animal ,Female ,medicine.symptom ,business ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
OBJECTIVE: Our purpose was to compare the effects of peptidyl and nonpeptidyl oxytocin antagonists on the pregnant rat uterus in relation to the progress of gestation. STUDY DESIGN: Pregnant rats with gestational ages of 17 and 21 days were used. A saturation binding of tritiated oxytocin to myometrial membrane preparation and its displacement by unlabeled oxytocin and the oxytocin antagonists were examined. The inhibitory effects of peptidyl and nonpeptidyl oxytocin on spontaneous, oxytocin-induced, and prostaglandin F 2α - induced uterine contractions were also evaluated in vitro and in vivo. RESULTS: The number of tritiated oxytocin binding sites in myometrial membranes of pregnant rats increased markedly at day 21 of gestation compared with day 17 of gestation, whereas the dissociation constants for tritiated oxytocin did not differ significantly. As for the binding affinities to oxytocin receptors of myometrial membranes, the inhibition constant values of nonpeptidyl oxytocin were 79 and 351 times larger than those of peptidyl oxytocin at pregnancy days 17 and 21, respectively. Both drugs remarkably inhibited oxytocin-induced uterine contractions in a dose-dependent manner. However, peptidyl oxytocin did not affect spontaneous and prostaglandin F 2α - induced contractions except for spontaneous ones of rats of pregnancy day 21 in vivo. On the other hand, nonpeptidyl oxytocin suppressed spontaneous and prostaglandin F 2α - induced contractions of the uterus both in vivo (pregnancy day 17) and in vitro (pregnancy day 21). CONCLUSION: These results suggest that peptidyl oxytocin may inhibit uterine contractions by selectively antagonizing the oxytocin action at the receptor site, whereas nonpeptidyl oxytocin at high concentrations may have the additional effect of directly suppressing the contractions. This effect of nonpeptidyl oxytocin may become therapeutically advantageous in clinical application for preterm labor. (Am J Obstet Gynecol 1996;175:1348-55.)
- Published
- 1996
12. Effects of KSG-504, a new CCK-A receptor antagonist, on gallbladder and gastrointestinal functions
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Masaru Sugiura, Mamoru Kobayashi, Yukiyoshi Ajisawa, Yoshinobu Yamazaki, Masuo Akahane, and Kazuhiko Shinagawa
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Male ,medicine.medical_specialty ,Gallbladder Emptying ,Duodenum ,Guinea Pigs ,In Vitro Techniques ,Naphthalenes ,digestive system ,Sincalide ,Gastric Acid ,Guinea pig ,Mice ,Internal medicine ,medicine ,Animals ,Rats, Wistar ,Pentanoic Acids ,Gastrin ,Pharmacology ,Mice, Inbred ICR ,Gastrointestinal tract ,Dose-Response Relationship, Drug ,Gastric emptying ,Chemistry ,Stomach ,Gallbladder ,digestive, oral, and skin physiology ,Muscle, Smooth ,Rats ,Receptor, Cholecystokinin A ,Endocrinology ,medicine.anatomical_structure ,Gastric Emptying ,Gastric acid ,Receptors, Cholecystokinin ,Rabbits ,hormones, hormone substitutes, and hormone antagonists ,Muscle Contraction - Abstract
We investigated the interaction of KSG-504 with CCK-8- or pentagastrin-induced gallbladder and gastrointestinal responses in vitro and in vivo. KSG-504 (10(-7)-10(-4) M) inhibited CCK-8-induced contractions of both isolated guinea pig gallbladder and rabbit terminal cavity of the bile duct in a concentration-dependent manner. Furthermore, intravenous administration of KSG-504 also dose-dependently inhibited CCK-8-induced gallbladder contraction in anesthetized guinea pigs with an IC50 value of 0.23 mg/kg. In conscious mice, KSG-504 inhibited both CCK-8- and egg yolk-stimulated gallbladder emptying in a dose-dependent manner (IC50: 13.3 and 9.6 mg/kg, respectively). The CCK-8-induced delay of gastric emptying in conscious rats was also antagonized by KSG-504 with an IC50 value of 3.78 mg/kg, i.v., whereas pentagastrin-stimulated gastric acid secretion in anesthetized rats was not affected by KSG-504 at all. KSG-504 (1 mg/kg, i.v.) also inhibited CCK-8-induced duodenal and jejunal contractions in anesthetized rabbits. These results indicate that KSG-504 exerts an antagonistic effect on CCK-A receptors in the gastrointestinal tract, but not on gastrin receptors in the stomach.
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- 1996
13. Effects of KSG-504, a New Cholecystokinin-A-Receptor Antagonist, on Pancreatic Exocrine and Endocrine Secretions in Rats
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Mamoru Kobayashi, Yukiyoshi Ajisawa, Yoshinobu Yamazaki, Hiroo Takeda, and Masuo Akahane
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Male ,medicine.medical_specialty ,Naphthalenes ,digestive system ,Sincalide ,Secretin ,Hormone Antagonists ,Internal medicine ,medicine ,Animals ,Endocrine system ,Amylase ,Rats, Wistar ,Pentanoic Acids ,Cholecystokinin A receptor ,Pancreas ,Cholecystokinin ,Pharmacology ,Dose-Response Relationship, Drug ,biology ,Pancreatic Exocrine Secretion ,Chemistry ,Trypsin ,Rats ,Endocrinology ,Pancreatic juice ,biology.protein ,Receptors, Cholecystokinin ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
The effects of KSG-504 ((S)-arginium (R)-4-[N-(3-methoxypropyl)-7V-pentylcarbamoyl]-5-(2-naphthylsulfonyl) pentanoate monohydrate), a new cholecystokinin (CCK)-A-receptor antagonist, on pancreatic exocrine secretion in anesthetized rats and endocrine secretion in conscious rats were studied. Intravenous injection of KSG-504 inhibited the pancreatic amylase output stimulated by intravenous infusion of CCK-8 in a dose-dependent manner (ED50: 18 μg/kg/min). Moreover, KSG-504 significantly reduced the CCK-8-stimulated increases in pancreatic juice volume and outputs of protein, trypsin and lipase. Intraduodenal infusion of casein increased the plasma CCK concentration and the pancreatic amylase output. KSG-504 significantly inhibited the pancreatic amylase output stimulated by casein. Pancreatic juice volume and bicarbonate output were significantly stimulated by intravenous infusion of secretin, but were not changed by KSG-504. When pancreatic exocrine secretion was stimulated by secretin plus CCK-8, KSG-504 suppressed the increases in juice volume and bicarbonate output to the level stimulated by secretin alone. Basal pancreatic amylase output was decreased by KSG-504. KSG-504 decreased the level of plasma immunoreactive insulin (IRI) stimulated by glucose plus CCK-8, but had no effect on IRI stimulated by glucose alone and the basal IRI. These in vivo studies suggest that KSG-504 has significant inhibitory effects both on the pancreatic exocrine and endocrine secretion stimulated by CCK, but has no effect on the exocrine secretion stimulated by secretin.
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- 1996
14. Effect of KSG-504, a new CCK-A-receptor antagonist, on experimental acute pancreatitis in rats and mice
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Masaru Sugiura, Kazuhiko Shinagawa, Tatsuya Nagasawa, Yukiyoshi Ajisawa, Masuo Akahane, and Mamoru Kobayashi
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Male ,medicine.medical_specialty ,Naphthalenes ,Cholecystokinin receptor ,Mice ,Internal medicine ,medicine ,Animals ,Amylase ,Rats, Wistar ,Lipase ,Pentanoic Acids ,Pancreas ,Cholecystokinin ,Pharmacology ,Mice, Inbred ICR ,Dose-Response Relationship, Drug ,biology ,business.industry ,Antagonist ,medicine.disease ,Rats ,Receptor, Cholecystokinin A ,Disease Models, Animal ,Endocrinology ,medicine.anatomical_structure ,Pancreatitis ,Acute Disease ,Amylases ,biology.protein ,Acute pancreatitis ,Receptors, Cholecystokinin ,business ,Ceruletide - Abstract
We investigated the protective and/or therapeutic effects of a new cholecystokinin receptor antagonist, KSG-504, on different types of experimental pancreatitis in the rat and mouse. The intravenous injection of KSG-504 (10, 25, 50 and 100 mg/kg) before caerulein administration to the rat inhibited the increases in plasma amylase, lipase and of pancreatic wet weight in a dose-dependent manner. The histological changes due to caerulein-induced acute pancreatitis were also decreased by KSG-504 when KSG-504 (25, 50 and 100 mg/kg) was administered after the induction of acute pancreatitis; the increases in plasma amylase, lipase and pancreatic wet weight were reduced, but the histological changes of the pancreas were not decreased significantly. In the second experiment, acute pancreatitis was induced in rats by injecting 0.3 ml of 6% sodium taurocholate into the pancreatic interstitial tissue. KSG-504 administered immediately and 1.5 hr after sodium-taurocholate injection at 100 mg/kg reduced the increases of pancreatic enzymes in the plasma, pancreatic wet weight and ascites. Moreover, KSG-504 (50 and 100 mg/kg, i.v., x 2) mitigated the histological changes of taurocholate-induced acute pancreatitis. Another type of acute pancreatitis was induced in mice by dl-ethionine (0.5 g/kg, p.o., x 4) and a choline-deficient diet. KSG-504 (10, 30 and 100 mg/kg) was subcutaneously administered five times every 12 hr during the experiment. KSG-504 elongated the survival of mice in a dose-dependent manner. These findings suggest that KSG-504 has potent protective and/or therapeutic effects against acute pancreatitis and that cholecystokinin may be involved in the development of pancreatitis.
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- 1996
15. Studies on the Synthesis of Cholecystokinin A Receptor Antagonists. II. Synthesis and Cholecystokinin A Receptor Inhibitory Activities of Sulfur-Containing Amide-Carboxylic Acid Derivatives
- Author
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Nakano Yasushi, Yukiyoshi Ajisawa, Makio Kitazawa, Kosuke Okazaki, Michihiro Kobayashi, Atsushi Tsubaki, Masaaki Ban, and Sato Kazuaki
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Male ,Stereochemistry ,Carboxylic acid ,Pharmaceutical Science ,In Vitro Techniques ,Sulfides ,Inhibitory postsynaptic potential ,Cholecystokinin receptor ,Structure-Activity Relationship ,chemistry.chemical_compound ,Amide ,Animals ,Sulfones ,Rats, Wistar ,Receptor ,Cholecystokinin A receptor ,Cholecystokinin ,Pharmacology ,chemistry.chemical_classification ,Chemistry ,digestive, oral, and skin physiology ,Sulfur containing ,Rats ,Receptor, Cholecystokinin A ,Sulfoxides ,Receptors, Cholecystokinin ,hormones, hormone substitutes, and hormone antagonists - Abstract
A number of sulfur-containing amide-carboxylic acid derivatives were synthesized and tested for cholecystokinin A (CCK-A) receptor inhibitory activity in order to study structure-activity relationships. Significant CCK-A receptor inhibitory activities were found in only two series, that is, sulfoxide-carboxylic acid derivatives (9) and sulfone-carboxylic acid derivatives (10). As the most preferred compound, 5-(3,4-dichlorophenylsulfonyl)-4-(N,N-dipentylcarbamoyl)pent anoic acid (10n) was selected.
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- 1996
16. Studies on the Synthesis of Cholecystokinin A Receptor Antagonists. I. Synthesis and Cholecystokinin A Receptor Inhibitory Activities of Malonamide Derivatives
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Yukiyoshi Ajisawa, Michihiro Kobayashi, Makio Kitazawa, and Masahiko Uchida
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Pharmacology ,Chemistry ,Stereochemistry ,digestive, oral, and skin physiology ,Pharmaceutical Science ,Inhibitory postsynaptic potential ,digestive system ,Malonates ,Structure-Activity Relationship ,Biochemistry ,Receptors, Cholecystokinin ,Cholecystokinin A receptor ,Receptor ,hormones, hormone substitutes, and hormone antagonists ,Cholecystokinin - Abstract
2-Substituted malonamide derivatives were synthesized and tested for cholecystokinin A (CCK-A) receptor inhibitory activity. Significant CCK-A receptor inhibitory activities were found in only three compounds (4g-i) which have carboxyl group. In order to study structure-activity relationships, carboxyethyl group was selected for 2-substituent and a number of N-substituted malonamides were prepared. After these compounds were tested for CCK-A receptor inhibitory activity, 4-(3,4-dichlorophenylcarbamoyl)-N,N-dipentylglutaramic acid (4h) was selected as the most preferred compound.
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- 1996
17. Effects of selective beta2 and beta3-adrenoceptor agonists on detrusor hyperreflexia in conscious cerebral infarcted rats
- Author
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Kouichi, Kaidoh, Yasuhiko, Igawa, Hiroo, Takeda, Yoshinobu, Yamazaki, Satoshi, Akahane, Hiroshi, Miyata, Yukiyoshi, Ajisawa, Osamu, Nishizawa, and Karl-Erik, Andersson
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Procaterol ,Rats, Sprague-Dawley ,Reflex, Abnormal ,Urinary Bladder ,Animals ,Adrenergic beta-3 Receptor Agonists ,Female ,Cerebral Infarction ,Dioxoles ,Adrenergic beta-Agonists ,Urinary Bladder, Neurogenic ,Adrenergic beta-2 Receptor Agonists ,Rats - Abstract
We evaluated the effects of beta-adrenoceptor agonists on detrusor hyperreflexia in cerebral infarcted rats.To produce cerebral infarction in Sprague-Dawley rats the left middle cerebral artery was occluded by introducing a monofilament nylon thread into the artery. In sham operated rats the same artery was exposed but not occluded. After these operations cystometric and cardiovascular experiments were performed with no anesthesia or restraint.After the operation bladder capacity was significantly decreased and voiding pressure was significantly increased in cerebral infarcted but not in sham operated animals. The difference in cerebral infarcted and sham operated rats was significant for each parameter (p0.01). Post-void residual urine volume was not affected in either group. In the cerebral infarction group intravenous administration of CL316243 ([R,R]-5-2-[[2-(3-chlorophenyl-2-hydroxyethyl]-amino]propyl] -1,3-benzodioxole-2,2-dicarboxylate) (Kissei Central Laboratories, Hotaka, Japan) a selective beta3-adrenoceptor agonist, significantly increased bladder capacity at 10 and 100 microgram./kg. without affecting voiding pressure or post-void residual urine volume. Procaterol, a selective beta2-adrenoceptor agonist, significantly increased bladder capacity and post-void residual urine volume at 10 microgram/kg. intravenously without affecting voiding pressure. In separate experiments procaterol (1 to 100 microgram./kg. intravenously) decreased mean blood pressure and increased heart rate in a dose dependent manner. In contrast, the effects of CL316243 (0.1 to 100 microgram./kg. intravenously) on mean blood pressure and heart rate were minimal.These results indicate that in cerebral infarcted rats detrusor hyperreflexia can be suppressed by the selective beta3-adrenoceptor agonist CL316243 without increasing post-void residual volume and without significant cardiovascular side effects. If the current results hold true in humans, selective beta3-adrenoceptor agonists may prove useful for treating detrusor hyperreflexia associated with cerebral infarction.
- Published
- 2002
18. Characterization of beta-adrenoceptor subtypes in the ferret urinary bladder in vitro and in vivo
- Author
-
Yasuhiko Igawa, Osamu Nishizawa, Hiroo Takeda, Yoshinobu Yamazaki, Yukiyoshi Ajisawa, Masuo Akahane, and Yoshimitsu Komatsu
- Subjects
Detrusor muscle ,Male ,medicine.medical_specialty ,Time Factors ,Procaterol ,Hydrochloride ,Muscle Relaxation ,Adrenergic beta-Antagonists ,Urinary Bladder ,Blood Pressure ,Dioxoles ,In Vitro Techniques ,Propanolamines ,chemistry.chemical_compound ,In vivo ,Heart Rate ,Internal medicine ,Isoprenaline ,Dobutamine ,Receptors, Adrenergic, beta ,medicine ,Pressure ,Animals ,Anesthesia ,Pharmacology ,Urinary bladder ,Dose-Response Relationship, Drug ,Antagonist ,Ferrets ,Isoproterenol ,Adrenergic beta-Agonists ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Ethanolamines ,medicine.drug - Abstract
In the present study, the β-adrenoceptor subtypes distributed in the detrusor of the ferret were investigated in functional experiments in vitro and in vivo using a variety of β-adrenoceptor agonists and antagonists. All the β-adrenoceptor agonists tested relaxed the isolated detrusor strip, the rank order of potency being (±)-( R *, R *)-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]phenoxy]-acetic acid sodium (BRL 37344A)>(±)-4-(3- t -butylamino-2-hydroxypropoxy) benzimidazol-2-one (CGP-12177A), isoprenaline and ( R , R )-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethylamino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL 316,243)>dobutamine and procaterol. In antagonist experiment, 3-(2-allylphenoxy)-1-[(1 S )-1,2,3,4-tetrahydro-naphth-1-ylamino]-(2 S )-2-propanol hydrochloride (SR 58894A), but neither 2-hydroxy-5(2-((2-hydroxy-3-(4-((1-methyl-4-trifluoromethyl)1 H -imidazole-2-yl)-phenoxy)propyl)amino)ethoxy)-benzamide monomethane sulphonate (CGP-20712A) nor erythro-(±)-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol hydrochloride (ICI-118,551), caused a rightward shift of the concentration-relaxation curve for isoprenaline. In in vivo experiments, isoprenaline and CL 316,243 each reduced bladder pressure in a dose-dependent manner. CL 316,243 was the only drug that did not produce any significant influences on blood pressure and heart rate at doses that reduced bladder pressure. The present functional study provides the first evidence that relaxation of the ferret detrusor by β-adrenoceptor activation is mediated mainly via the β 3 -adrenoceptor, as in the human detrusor.
- Published
- 2000
19. Role of oxytocin in the initiation of term and preterm labor in rats: changes in oxytocin receptor density and plasma oxytocin concentration and the effect of an oxytocin antagonist, L-366,509
- Author
-
Masuo Akahane, Mamoru Kobayashi, Keiko Minami, Tatsuhiko Kawarabayashi, Makoto Moro, Yukiyoshi Ajisawa, and Yoshihito Inoue
- Subjects
medicine.medical_specialty ,Oxytocin ,Oxytocin Antagonist ,Rats, Sprague-Dawley ,Hormone Antagonists ,Obstetric Labor, Premature ,Piperidines ,Pregnancy ,Internal medicine ,Blood plasma ,medicine ,Animals ,Spiro Compounds ,reproductive and urinary physiology ,Progesterone ,Morning ,Labor, Obstetric ,Dose-Response Relationship, Drug ,business.industry ,Antagonist ,Obstetrics and Gynecology ,medicine.disease ,Oxytocin receptor ,Rats ,Endocrinology ,Receptors, Oxytocin ,Gestation ,Female ,business ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Objective: Our purpose was to compare the functional roles of oxytocin in term and preterm labor in rats by both biochemical and pharmacologic means. Study Design: We determined the myometrial oxytocin receptor density and the maternal plasma concentrations of oxytocin and progesterone on gestational days 18, 20, and 22 (morning) and at the onset of delivery (day 22 afternoon) in rats with labor at term and at the onset of delivery (day 20 afternoon) in rats in preterm labor induced by the combined use of bilateral ovariectomy and estradiol injection. We also evaluated the effects of an oxytocin antagonist, L-366,509, on the initiation of both term and preterm labor. Results: The number of tritiated oxytocin binding sites in myometrial membranes rapidly increased on gestational day 22 (morning) in rats with term labor. Plasma progesterone level decreased in an inverse fashion. A rapid increase in circulating oxytocin concentration was observed at the onset of delivery in rats in labor at term. Both the plasma oxytocin concentration and the receptor density had the same values in rats with preterm labor as in rats with term labor. L-366,509 delayed the initiation of labor in rats with term and preterm labor in a dose-dependent manner. Conclusion: It is confirmed biochemically and pharmacologically that oxytocin plays an important role in the initiation of both term and preterm labor in rats. The oxytocin antagonist examined was able to delay term and preterm labor, so it might prove useful in clinical practice for the treatment of preterm labor. (Am J Obstet Gynecol 1999;180:621-7.)
- Published
- 1999
20. Regulation of interleukin-1beta-induced interleukin-6 gene expression in human fibroblast-like synoviocytes by p38 mitogen-activated protein kinase
- Author
-
Hirokazu Okudaira, Hiroshi Miyata, Yukiyoshi Ajisawa, Keiji Miyazawa, Akio Mori, and Masuo Akahane
- Subjects
Pyridines ,MAPK7 ,Anti-Inflammatory Agents ,Mitogen-activated protein kinase kinase ,Protein Serine-Threonine Kinases ,Biochemistry ,p38 Mitogen-Activated Protein Kinases ,MAP2K7 ,Arthritis, Rheumatoid ,Osteoarthritis ,Humans ,ASK1 ,c-Raf ,Cycloheximide ,Molecular Biology ,Cells, Cultured ,MAPK14 ,Cell Nucleus ,MAP kinase kinase kinase ,Dose-Response Relationship, Drug ,Chemistry ,Interleukin-6 ,Synovial Membrane ,Imidazoles ,Intracellular Signaling Peptides and Proteins ,NF-kappa B ,Cell Biology ,Fibroblasts ,Molecular biology ,Recombinant Proteins ,Kinetics ,Gene Expression Regulation ,Calcium-Calmodulin-Dependent Protein Kinases ,Dactinomycin ,Cyclin-dependent kinase 9 ,Mitogen-Activated Protein Kinases ,Interleukin-1 - Abstract
Involvement of p38 mitogen-activated protein (MAP) kinase in interleukin (IL)-6 gene expression of human fibroblast-like synoviocytes (FLSs) was assessed. p38 MAP kinase was constitutively expressed in human FLSs and activated in response to IL-1beta. A pyridinylimidazole compound, SB203580, inhibited p38 MAP kinase activity in vivo, since the activity of MAPKAP kinase-2 (a substrate of p38 MAP kinase) in IL-1beta-stimulated FLSs was totally suppressed by it. SB203580 concentration-dependently inhibited protein production and gene expression of IL-6 by human FLSs. The effect of SB203580 was dependent on de novo protein synthesis. SB203580 significantly reduced the stability of IL-6 mRNA without affecting the rate of IL-6 gene transcription. Here, we provide evidence that p38 MAP kinase is activated in response to IL-1beta in human FLSs and is involved in IL-6 synthesis by stabilizing IL-6 mRNA.
- Published
- 1998
21. Inhibition by tranilast of vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF)-induced increase in vascular permeability in rats
- Author
-
Hiroshi Miyata, Masayuki Isaji, Yukiyoshi Ajisawa, and Nagahisa Yoshimura
- Subjects
Male ,Vascular Endothelial Growth Factor A ,Angiogenesis ,Tranilast ,VEGF receptors ,Vascular permeability ,Endothelial Growth Factors ,Pharmacology ,General Biochemistry, Genetics and Molecular Biology ,Capillary Permeability ,Rats, Sprague-Dawley ,Vascular Permeability Factor ,chemistry.chemical_compound ,medicine ,Animals ,ortho-Aminobenzoates ,General Pharmacology, Toxicology and Pharmaceutics ,Lymphokines ,biology ,Dose-Response Relationship, Drug ,Vascular Endothelial Growth Factors ,Air pouch ,General Medicine ,Rats ,Vascular endothelial growth factor ,chemistry ,biology.protein ,medicine.drug - Abstract
We studied the effects of tranilast, an anti-allergic and anti-proliferative drug in clinical use, on VEGF/VPF-induced vascular permeability in a rat air pouch model. A large increase in vascular permeability was induced by injection of 4 ml of a 100 ng/ml VEGF/VPF solution into the preformed air pouch. Over a 15-min period, tranilast inhibited the VEGF/VPF-induced vascular permeability in a dose-dependent manner. This result suggests that tranilast, which we recently found to inhibit VEGF/VPF-induced angiogenesis, could also improve VEGF/VPF-dependent increases in vascular permeability.
- Published
- 1998
22. [Studies on the synthesis of cholecystokinin A receptor antagonists. III. Synthesis and cholecystokinin A receptor inhibitory activities of naphthyl sulfone derivatives]
- Author
-
Makio Kitazawa, Atsushi Tsubaki, Kosuke Okazaki, Masahiko Uchida, Masaaki Ban, Yukiyoshi Ajisawa, Sato Kazuaki, Nakano Yasushi, and Michihiro Kobayashi
- Subjects
Pharmacology ,Male ,Stereochemistry ,digestive, oral, and skin physiology ,Pharmaceutical Science ,In Vitro Techniques ,Naphthalenes ,Inhibitory postsynaptic potential ,Sulfone ,Rats ,Receptor, Cholecystokinin A ,chemistry.chemical_compound ,Structure-Activity Relationship ,chemistry ,Michael reaction ,Structure–activity relationship ,Animals ,Receptors, Cholecystokinin ,Sulfones ,Rats, Wistar ,Cholecystokinin A receptor ,Receptor ,hormones, hormone substitutes, and hormone antagonists ,Cholecystokinin - Abstract
A number of naphthyl sulfone derivatives were synthesized and tested for cholecystokinin A (CCK-A) receptor inhibitory activity in order to study structure-activity relationships. Significant CCK-A receptor inhibitory activities were found in sulfone-carboxylic acid derivatives (7) having very hydrophobic sidechains. As the most preferred compound, (R)-4-[N-(3-methoxypropyl)-N-pentylcarbamoyl]-5-(2-naphthylsulf onyl) pentanoic acid ((R)-7c) was selected.
- Published
- 1996
23. Effect of a non-sulphonylurea hypoglycaemic agent, KAD-1229 on hormone secretion in the isolated perfused pancreas of the rat
- Author
-
Hideki Ohnota, Mayumi Kinukawa, and Yukiyoshi Ajisawa
- Subjects
medicine.medical_specialty ,endocrine system ,Indoles ,Somatostatin secretion ,medicine.medical_treatment ,Biology ,Isoindoles ,Glucagon ,Streptozocin ,Internal medicine ,Insulin Secretion ,medicine ,Animals ,Hypoglycemic Agents ,Insulin ,Pancreas ,Pharmacology ,Glucagon secretion ,Streptozotocin ,Anti-Bacterial Agents ,Rats ,Somatostatin ,medicine.anatomical_structure ,Endocrinology ,Glucose ,Basal (medicine) ,Reperfusion ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug ,Research Article - Abstract
1. We examined the cooperative effect of a newly synthesized oral hypoglycaemic agent, KAD-1229 with glucose on insulin, glucagon and somatostatin secretion in the isolated perfused pancreas of the rat. 2. KAD-1229 stimulated concentration-dependently the first phase of insulin secretion without the second phase in the presence of 2.8 mM glucose, while it stimulated both the first and the second phase of insulin release in the presence of 5.6 mM glucose. It was confirmed that the first phase of insulin release is depolarization-induced release with no other additional signal transduction. 3. KAD-1229 also enhanced insulin release evoked by 16.7 mM glucose, a concentration known to inhibit the ATP-sensitive K+ current completely. 4. A low concentration (2.8 mM) of glucose stimulated somatostatin release transiently, while a higher concentration (16.7 mM) of glucose exerted a sustained stimulation. KAD-1229 stimulated somatostatin secretion in a concentration-dependent manner irrespective of glucose concentrations. 5. When glucagon release was stimulated with 2.8 mM glucose, KAD-1229 inhibited this hypoglycaemia-induced glucagon secretion. 6. When pancreata from rats pretreated with streptozotocin (STZ) 60 mg kg-1 were perfused, the basal secretion of glucagon was markedly elevated, and the glucagon response to the low glucose was abolished. Further, the insulin and somatostatin responses to KAD-1229 were largely attenuated. KAD-1229 showed transient enhancement followed by inhibition of the glucagon release from the STZ-pretreated rat pancreas. 7. We conclude that KAD-1229 stimulates insulin and somatostatin release, while it inhibits glucagon release following transient stimulation.
- Published
- 1996
24. [Behavioral studies of KSG-504, a new CCK-A receptor antagonist]
- Author
-
Atsushi Tsubaki, Yoshinobu Yamazaki, Masuo Akahane, Yukiyoshi Ajisawa, and Hiroo Takeda
- Subjects
Drug ,Male ,media_common.quotation_subject ,Pharmacology ,Motor Activity ,Naphthalenes ,Sincalide ,Mice ,Cerebrospinal fluid ,Dogs ,Medicine ,Animals ,Rats, Wistar ,Thiopental ,Receptor ,Pentanoic Acids ,CCK-A Receptor ,media_common ,Mice, Inbred ICR ,Behavior, Animal ,business.industry ,Antagonist ,Drug Synergism ,Peripheral ,Rats ,Receptor, Cholecystokinin A ,Vomiting ,Female ,Receptors, Cholecystokinin ,Rabbits ,medicine.symptom ,business ,Antagonism - Abstract
The effects of KSG-504 after intravenous administration on behavior and other central functions were studied. KSG-504 did not affect the general behavior of dogs up to the dose of 30 mg/kg, but the drug (100 mg/kg, i.v.) caused vomiting in 3 out of the 5 dogs. Moreover, KSG-504 (1-30 mg/kg, i.v.) had no effects on spontaneous motility, thiopental-induced sleep, acetic acid-induced writhing in mice and satiety in rats. A high dose of CCK-8 (100 micrograms/kg or more) suppressed spontaneous motility, writhing and satiety, and prolonged sleep when administered subcutaneously. The behavioral changes induced by CCK-8 were antagonized by KSG-504 in a dose-dependent manner (1-30 mg/kg, i.v.). When KSG-504 was administered intravenously to rabbits at the dose of 10 mg/kg or 0.5 mg/kg/min for 120 min, we could not detect the drug in the cerebrospinal fluid, indicating that KSG-504 does not cross the blood-brain barrier after peripheral administration of the drug. Thus, the inhibitory effect of KSG-504 on CCK-8-induced behavioral changes may be the result of antagonism at peripheral CCK-A receptors.
- Published
- 1996
25. Cholecystokinin-A specific antagonism of KSG-504 to cholecystokinin receptor binding and pancreatic secretion in mammals
- Author
-
Yukiyoshi Ajisawa, Yoshinobu Yamazaki, Mamoru Kobayashi, Hiroo Takeda, Masuo Akahane, and Kazuhiko Shinagawa
- Subjects
Male ,medicine.medical_specialty ,Vasoactive intestinal peptide ,Biology ,Naphthalenes ,digestive system ,Cholecystokinin receptor ,Binding, Competitive ,Sincalide ,Radioligand Assay ,Hormone Antagonists ,Internal medicine ,Gastric glands ,Cholecystokinin receptor binding ,medicine ,Animals ,Amylase ,Rats, Wistar ,Pentanoic Acids ,Pancreas ,Cholecystokinin ,Pharmacology ,Dose-Response Relationship, Drug ,Ligand binding assay ,digestive, oral, and skin physiology ,Rats ,medicine.anatomical_structure ,Endocrinology ,Amylases ,biology.protein ,hormones, hormone substitutes, and hormone antagonists - Abstract
The effects of KSG-504 ((S)-arginium (R)-4-[-N-(3-methoxypropyl)-Ar-pentylcarbamoyl]-5-(2-naphthylsulfonyl) pentanoate monohydrate), a new cholecystokinin (CCK)-receptor antagonist, onl25I-CCK-8 binding to rat pancreatic, canine gallbladder and guinea pig cerebrocortical membranes and the pancreatic amylase release from isolated rat acini stimulated by several kinds of secretagogues, including CCK, were investigated. The125I-CCK-8 saturation experiment showed that pancreatic, gallbladder and cerebrocortical CCK receptors had a single high affinity binding component with dissociation constants (Kd) of 0.18, 0.31 and 0.88 nM, respectively. The maximum numbers of specific binding sites (Bmax) in these membranes were 1012, 52 and 20 fmol/mg protein, respectively. KSG-504 and CCK-8 displaced specific125I-CCK-8 binding to CCK receptors in all membrane preparations in a competitive manner. The affinity of KSG-504 for pancreatic (Ki= 173 nM) and gallbladder (Ki = 283 nM) CCK receptors were >3 orders of magnitude higher than its affinity for cerebrocortical CCK receptors. KSG-504 also inhibited125I-gastrin-I binding to guinea pig gastric glands, but the IC50 value (18.2 μΜ) was apparently much higher. CCK-8-stimulated amylase release from isolated pancreatic acini of rats was antagonized by KSG-504 in a concentration-dependent manner. KSG-504 did not affect amylase release stimulated by secretagogues such as gastrin-releasing peptide, carbachol, vasoactive intestinal peptide and A23187. These results indicate that KSG-504 acts as a CCK-A-receptor-specific antagonist in the pancreas and gallbladder.
- Published
- 1995
26. THE EFFECTS OF A NOVEL BETA2/BETA3 ADRENOCEPTOR AGONIST KUL-1248 ON THE URETERAL MOTILITY IN VITRO AND IN VIVO
- Author
-
Makoto Murakami, Yukiyoshi Ajisawa, Yoshitaka Tomiyama, Young-Chol Park, Takashi Kurita, Kohichi Hayakawa, and Masuo Akahane
- Subjects
business.industry ,In vivo ,Urology ,Medicine ,Motility ,Pharmacology ,Adrenoceptor agonist ,business ,In vitro - Published
- 1999
27. Selective inhibition of uterine contraction by KUR-1247
- Author
-
Koichi Kaido, Mamoru Kobayashi, Keiko Minami, Makoto Moro, Masuo Akahane, and Yukiyoshi Ajisawa
- Subjects
Pharmacology ,Chemistry ,medicine ,Selective inhibition ,medicine.symptom ,Uterine contraction - Published
- 1998
28. pharmacological evidence for a β3-adrenoceptor in the ferret ureter
- Author
-
Yoshitaka Tomiyama, Masuo Akahane, Kazuhiko Shinagawa, Kohichi Hayakawa, and Yukiyoshi Ajisawa
- Subjects
Pharmacology ,medicine.medical_specialty ,Ureter ,medicine.anatomical_structure ,business.industry ,Urology ,Medicine ,β3 adrenoceptor ,business - Published
- 1998
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