Search

Impaired epithelial barrier function disrupts immune homeostasis and increases inflammation in intestines, leading to many intestinal diseases. The blend of organic acids (OAs) and medium chain fatty acids (MCFAs) has been shown to have synergistic bactericidal effect. In this study, we demonstrated that two blends of OAs and MCFAs (OM1 and OM2) could prevent the inflammatory response and intestinal barrier dysfunction in enterohemorrhagic Escherichia coli (EHEC)-infected mice. Treatments of OM1 and OM2 significantly reduced the body weight loss and production of IL-6 and TNF-α induced by EHEC. Mice treated with OM1 and OM2 showed decrease in serum D-lactic concentration, DAO activity and bacterial transfer to liver and spleen. Furthermore, OM1 and OM2 increased the expression of tight junction proteins occludin and ZO-1, mucus protein MUC-2, and host defense peptides mBD1, mBD2 and mBD3. Finally, OM1 and OM2 increased the population of Lactobacillus spp. and Bifidobacterium spp., but decreased that of E. coli in the cecum. These findings indicate that OM1 and OM2 may be used to develop a prophylactic agent for intestinal inflammation and injury in enteric pathogen infection., (Copyright © 2018. Published by Elsevier B.V.)

Although it is well-known that retrograde transport of urine fills the caeca of birds with fluid and small particles, the function of avian caeca is still not fully understood. We measured mean retention times (MRT) of solute (cobalt-EDTA, Co), small particle (<2mm, chromium-mordanted fibre, Cr) and large particle (8mm, cerium-marked fibre, Ce) markers in geese (Anser anser) and turkeys (Meleagris gallopavo) fed alfalfa pellets ad libitum. Intake did not differ between species. Turkeys had longer MRT for all markers (Co: 10.4 vs. 3.2h; Cr 23.3 vs. 2.9h; Ce 9.5 vs. 2.1h), achieved a higher fibre digestibility, and had a higher calculated dry matter gut fill. Thus, geese and turkeys correspond to the typical dichotomy of good fliers vs. poor fliers/flightless species in avian herbivores. Because uric acid is fermented much faster by microbes than fibre, the ultimate cause of short-MRT digesta retention in avian caeca as in geese is possibly rather uric acid than fibre fermentation. The numerical differences between marker MRT in geese correspond to a colonic separation mechanism that delays the excretion of fluids more than small and again more than large particles. In contrast to geese, turkeys excreted solid and liquid (caecal) faeces. Liquid faeces contained less fibre and more crude protein than solid faeces and accounted for the excretion of 7, 25 and 34% of Ce, Co and Cr markers. Marker excretion patterns and MRT for liquid faeces (Co 15 vs. Cr 50h) suggest that small particles did not simply move in parallel to fluids, but were retained selectively by being trapped in colonic digesta upon expulsion from caeca, with subsequent repeated retrograde transport into caeca with the next batch of urine. Given the absence of coprophagy in birds (in contrast to small mammalian herbivores), such a delay of small (microbial) particle escape from the caeca appears reasonable., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Hydrogen sulphide (H(2)S) is an endogenous mediator producing a potent relaxation response in vascular and non-vascular smooth muscles. While ATP-sensitive potassium channels are mainly involved in this relaxant effect in vascular smooth muscle, the mechanism in other smooth muscles has not been revealed yet. In the present study, we investigated how H(2)S relaxes non-vascular smooth muscle by using intact and β-escin permeabilized guinea-pig taenia caecum. In intact tissues, concentration-dependent relaxation response to H(2)S donor NaHS in carbachol-precontracted preparations did not change in the presence of a K(ATP) channel blocker glibenclamide, adenylate cyclase inhibitor SQ-22536, guanylate cyclase inhibitor ODQ, protein kinase A inhibitor KT-5720, protein kinase C inhibitor H-7, tetrodotoxin, apamin/charybdotoxin, NOS inhibitor L-NAME and cyclooxygenase inhibitor indomethacin. We then studied how H(2)S affected carbachol- or Ca(2+)-induced contractions in permeabilized tissues. When Ca(2+) was clamped to a constant value (pCa6), a further contraction could be elicited by carbachol that was decreased by NaHS. This decrease in contraction was reversed by catalase but not by superoxide dismutase or N-acetyl cysteine. The sarcoplasmic reticulum Ca(2+)-ATPase pump inhibitor, cyclopiazonic acid, also decreased the carbachol-induced contraction that was further inhibited by NaHS. Mitochondrial proton pump inhibitor carbonyl cyanide p-trifluromethoxyphenylhydrazone also decreased the carbachol-induced contraction but this was not additionally changed by NaHS. The carbachol-induced Ca(2+) sensitization, calcium concentration-response curves, IP(3)- and caffeine-induced contractions were not affected by NaHS. In conclusion, we propose that hydrogen peroxide and mitochondria may have a role in H(2)S-induced relaxation response in taenia caecum., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The mechanisms responsible to the development of brain dysfunction during sepsis are not well understood. The objective of this study is to evaluate mitochondrial respiratory chain and creatine kinase activities in the brain after cecal ligation and perforation (CLP) in rats. We performed a prospective, controlled experiment in male Wistar rats. Rats were subjected to CLP (sepsis group) with saline resuscitation (at 50mL/kg immediately and 12h after cecal ligation and perforation) or sham operation (control group). Several times (0, 6, 12, 24, 48 and 96h) after CLP six rats were killed by decapitation, and brain structures (cerebellum, hippocampus, striatum and cortex) were isolated. Mitochondrial respiratory chain and creatine kinase activity were then measured. It was observed that animals submitted to CLP presented decreased mitochondrial respiratory chain activity in complex I, but not in complex II, III and IV, 24, 48 and 96h in all analyzed structures. Activity of succinate dehydrogenase was decreased in 48 and 96h in all analyzed structures. Creatine kinase activity increased after CLP in cerebellum, hippocampus and cortex (after 0h) and striatum (after 6h). Sepsis associated brain injury may include dysfunction in the mitochondrial respiratory chain activity.

Using conventional microelectrode recording techniques, we investigated, in the circular muscle of the mouse caecum, the neurotransmitter(s) involved in the neurally-evoked inhibitory junction potentials (IJPs) and the existence of possible prejunctional mechanisms controlling neurotransmitter release. Electrical field stimulation with single pulses elicited IJPs, consisting only of a "fast" hyperpolarization, while using train stimuli (30-50 Hz) the initial fast hyperpolarization was followed by a slower hyperpolarization. The fast and the slow component were selectively antagonized by apamin, a blocker of calcium-activated potassium channels, and N(omega)-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase inhibitor, respectively. Fast IJPs were antagonized also by P2 purinoceptor antagonists, suramin or 4-[[4-formyl-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]-2-pyridinyl]azo]-1,3-benzenedisulfonic acid tetrasodium salt (PPADS), P2Y purinoceptor desensitization by adenosine 5'-O-2-thiodiphosphate (ADPbetaS). 2'-Deoxy-N(6)-methyl ADP diammonium salt (MRS 2179), P2Y1 purinoceptor antagonist, at the concentration of 1 microM increased the amplitude of the fast IJP, while at the concentration of 10 microM induced a reduction. 8,8'-[Carbonylbis[imino-3,1-phenylenecarbonylimino (4-fluoro-3,1-phenylene) carbonylimino]] bis-1,3,5-naphthalenetrisulfonic acid hexasodium salt (NF 157) and 2,2-dimethyl-propionic acid 3-(2-chloro-6-methylaminopurin-9-yl)-2-(2,2-dimethyl-propionyl-oxymethyl)-propyl ester (MRS 2395), P2Y11 and P2Y12 purinoceptor antagonist, were without any effect. ATP-induced hyperpolarization was affected by apamin and by P2Y purinoceptor desensitization, but not by MRS 2179. 2-(Methylthio)ATP tetrasodium salt hydrate (2-MeSATP), P2Y1 purinoceptor agonist, at a concentration which did not cause changes in the membrane potential, reduced the amplitude of the fast IJPs. This effect was prevented by MRS 2179. Paired nerve stimulation, either using single pulses or train stimuli, did not cause any alteration of the second-evoked IJP. In conclusion, in the circular muscle of the mouse caecum, ATP is responsible for the fast IJP while nitric oxide is responsible for the slow IJP. ATP-mediated response is dependent on ADPbetaS-sensitive P2Y receptors, which are in part P2Y1, but not P2Y11 or P2Y12 receptor subtypes. In addition, the most substantial finding of this study is the functional demonstration that ATP released by nerve stimulation activates P2Y1 receptors, located prejunctionally, limiting its release by motoneurons.

As gut capacity is assumed to scale linearly to body mass (BM), and dry matter intake (DMI) to metabolic body weight (BM(0.75)), it has been proposed that ingesta mean retention time (MRT) should scale to BM(0.25) in herbivorous mammals. We test these assumptions with the most comprehensive literature data collations (n=74 species for gut capacity, n=93 species for DMI and MRT) to date. For MRT, only data from studies was used during which DMI was also recorded. Gut capacity scaled to BM(1.06). In spite of large differences in feeding regimes, absolute DMI (kg/d) scaled to BM(0.76) across all species tested. Regardless of this allometry inherent in the dataset, there was only a very low allometric scaling of MRT with BM(0.14) across all species. If species were divided according to the morphophysiological design of their digestive tract, there was non-significant scaling of MRT with BM(0.04) in colon fermenters, BM(0.08) in non-ruminant foregut fermenters, BM(0.06) in browsing and BM(0.04) in grazing ruminants. In contrast, MRT significantly scaled to BM(0.24) (CI 0.16-0.33) in the caecum fermenters. The results suggest that below a certain body size, long MRTs cannot be achieved even though coprophagy is performed; this supports the assumption of a potential body size limitation for herbivory on the lower end of the body size range. However, above a 500 g-threshold, there is no indication of a substantial general increase of MRT with BM. We therefore consider ingesta retention in mammalian herbivores an example of a biological, time-dependent variable that can, on an interspecific level, be dissociated from a supposed obligatory allometric scaling by the morphophysiological design of the digestive tract. We propose that very large body size does not automatically imply a digestive advantage, because long MRTs do not seem to be a characteristic of very large species only. A comparison of the relative DMI (g/kg(0.75)) with MRT indicates that, on an interspecific level, higher intakes are correlated to shorter MRTs in caecum, colon and non-ruminant foregut fermenters; in contrast, no significant correlation between relative DMI and MRT is evident in ruminants.

Intracellular Ca2+ stores in rat and guinea-pig bladders and taenia caecum were studied in beta-escin skinned smooth muscle strips. 30 min of skinning with 40 microM and 80 microM beta-escin were the best parameters found to obtain good calcium response curves (10(-7)-10(-4) M) in rat and guinea pig, respectively. Calmodulin (1 microM) increased the calcium contractions significantly. pCa 6 was used to load intracellular stores and application of carbachol (50 microM) in all tissues then only contracted the tissues in the presence of guanosine-5'-triphosphate (GTP; 100 microM). Inositol triphosphate (IP3; 50 microM), applied after pCa 6, contracted all tissues. Carbachol added after IP3 or heparin (1 mg/ml) no longer caused a contraction in any of them. In bladders, caffeine (30 mM) but not ryanodine (5 microM) prevented the subsequent carbachol contraction. A slowly rising contraction with carbachol was elicited after caffeine (30 mM) or ryanodine (5 microM) in the taenia and after ryanodine in the bladders. Caffeine (30 mM) suppressed the calcium response curves in all tissues. Procaine (30 mM) blocked the carbachol (50 microM) contractions in bladders but not in taenia. These results suggest that calcium induced calcium release (CICR) and IP3 induced calcium release (IICR) release calcium from a common store in bladder but two different compartments in taenia.

We compared the effect of diets containing different nondigestible carbohydrates: cellulose (C), inulin (IN) and carboxymethylcellulose (CMC) as single supplements or in dietary combination on caecal physiology of rats. Sixty male Wistar rats (Rattus norvegicus) were divided into five groups and for 4 weeks were fed a casein diet with the compared carbohydrates (4% of diet) or a combination of IN+C or IN+CMC (both 4+4%). Diet intake and FCR index remained unaffected by the treatments, whereas IN improved the body weight gain of rats compared to CMC. Compared to C group, all diets containing IN and CMC decreased the caecal pH as well as enlarged the caecum, thus increasing the weights of contents and tissue, especially upon CMC treatment. Rats given carboxymethylcellulose (CMC and IN+CMC groups) had watery caecal digesta, and some of them suffered from diarrhoea. In the case of CMC, the caecal enlargement was due to tissue hypertrophy and digesta accumulation mostly in response to an increased bulk of contents. Unlike C+IN, the dietary combination of CMC- and inulin-enhanced fermentation in the caecum of rats, however the proportion of acetate, propionate and butyrate was less beneficial. Compared to CMC, inulin gave a higher concentration of SCFA, especially of butyrate and propionate. The action of inulin in the caecum of rats could be pronounced by dietary treatment combined with CMC.

Objective: It is believed that solid particles are not responsible for digesta viscosity. However, solid particles are responsible for the viscosity of whole blood and fiber suspension such as wood pulp. Therefore, we measured viscosity of gut contents with and without solid particles. We also determined the contribution of solid particles to viscoelastic characters of gut contents., Methods: We measured the coefficient of viscosity, shear rate, and shear stress of pig cecal contents by using a tube-flow viscometer before and after removal of particles., Results: The coefficient of viscosity of intact pig cecal contents was negatively correlated with shear rate, a typical character of non-Newtonian fluids. The removal of solid particles from the contents resulted in a Newtonian fluid with very low viscosity., Conclusion: Solid particles were mainly responsible for the viscoelastic character of pig cecal contents. Accordingly, the contribution of indigestible solid food components, sloughed epithelial cells, and bacterial cell bodies to the viscosity of gut contents should be re-evaluated.

The effect of atropine (1 microM) and N(G)-nitro-L-arginine (L-NOARG, 10 microM) on electrical field stimulation induced relaxation in proximal and distal segments of guinea-pig taenia caeci in the presence of guanethidine (4 microM) was studied. The frequency-dependent relaxations were lower in proximal than in distal segments both in the presence and in the absence of atropine. The effect of L-NOARG (an inhibitor of nitric oxide (NO) synthase) on relaxation in the presence of atropine depended on the frequency of electrical stimulation and the segment used; the effect of L-NOARG was greater in proximal segments than in distal segments. In the absence of atropine, the inhibitory effect of L-NOARG was the same in both segments at all frequencies tested. This study demonstrates differences between the opposite extremes of guinea-pig taenia caeci in relaxations induced by electrical stimulation. Our data also show a role of NO that is dependent on the integrity of cholinergic transmission.

Contraction of the guinea pig taenia caeci is mediated by muscarinic M3 receptors; however, they comprise only 30% of the muscarinic receptors present. This study investigated the role of the predominant M2 receptor population in contractions and possible second messengers involved after M3 receptors were selectively alkylated by 4-DAMP mustard [N-(2-chloroethyl)-4-piperidinyldiphenylacetate] (60 nM) in the presence of otenzepad (AF-DX 116; 1 microM). Concentration-response curves to oxotremorine-M (oxo-M) in the presence of histamine and isoprenaline were performed in the presence of otenzepad (1 and 3 microM), resulting in a mean apparent pK(B) of 6.49, indicative of an M2 response. As the taenia has intrinsic tone, precontraction with histamine was not necessary and, therefore, in some experiments only isoprenaline was included. In these studies, an M3 response to oxo-M was observed, as the mean apparent pK(B) for otenzepad was 5.89. To investigate protein kinase C (PKC) involvement in the M2 response following M3 inactivation, the inhibitor chelerythrine (1 microM) was included with histamine and isoprenaline in the absence and presence of otenzepad. The oxo-M concentration-response curve was shifted by otenzepad with an apparent pK(B) value of 6.05, a value significantly different from that seen in the absence of chelerythrine (P < 0.05). These results suggest that activation of PKC by a spasmogen such as histamine is necessary to see an M2 response following M3 receptor inactivation.

Crib-biting in the horse is frequently prevented in the short-term by horse-owners using physical means. Because it has been proposed that crib-biting may function to reduce stress, the effect of prevention of crib-biting and/or eating on the behaviour, heart rate, and plasma cortisol and beta-endorphin concentrations was measured in six crib-biting and six normal horses. When crib-biters were unable to crib-bite, they showed an increase in ingestive behaviour. When crib-biters were prevented from crib-biting and eating, a relative stasis in the motility of the foregut occurred, suggesting that normal gut function in these animals depends on ad libitum access to food and to suitable crib-biting substrates. There was no significant difference in the mean baseline levels of normal and crib-biting horses but, contrary to expectations, beta-endorphin levels were higher in crib-biting horses than in normal horses when crib-biting was prevented. Mean baseline levels of cortisol were higher, under a variety of test and control conditions, in crib-biting than in normal horses, but there was no significant rise in cortisol levels in crib-biters during periods when crib-biting was prevented, suggesting that the function of this oral stereotypy does not lie in stress-reduction.

Beta-adrenoceptor-mediated relaxation of guinea pig taenia caecum was investigated by studying the effects of the beta3-adrenoceptor agonists, BRL37344A [(R*,R*)-(+/-)-4-[2'-[2-hydroxy-2-(3-chlorophenyl) ethylamino] propyl] phenoxyacetic acid sodium salt sesquihydrate] and BRL35135A [(R*,R*)-(+/-)-methyl-4-[2-[2-hydroxy-2-(3-chlorophenyl) ethylamine] propyl] phenoxyacetate hydrobromide]. BRL37344A and BRL35135A caused dose-dependent relaxation of the guinea pig taenia caecum. The concentration-response curves for BRL37344A and BRL35135A were unaffected by propranolol, ICI118551 [erythro-1-(7-methylindan-4-yloxy)-3-(isopropylamine)-but an-2-ol], atenolol, butoxamine, prazosin, yohimbine and phentolamine. Bupranolol produced shifts of the concentration-response curves for BRL37344A and BRL35135A. Schild regression analyses carried out for bupranolol against BRL37344A and BRL35135A gave pA2 values of 5.79 and 5.84, respectively. These results suggest that the relaxant response to BRL37344A and BRL35135A of the guinea pig taenia caecum is mediated by beta3-adrenoceptors.

To study cecal motility and its relation to the fed and fasted condition in domestic fowl, we sutured 7 miniature electrodes onto the ceca and ileum of 4 roosters. After recovery from the surgery, the birds received recordings of myoelectric activity for a total of 169 h while fasted and for 28 h while in the fed state. We found that single or brief clusters of action potentials (APs) occurred in the cecal smooth muscle at mean frequencies of 10.8 to 25.0/h, with the fewest when the lumen contained little food (after fasting > 24 h). Virtually all APs propagated, whether orad (toward the ileocecocolic junction) or retrograde (toward the cecal tip), with retrograde activity significantly more frequent (P < 0.001). Propagation velocity was rapid, varying from 8 to 750 cm/min (mean = 106 cm/min), being slower when birds were in the fed state. Thus, fasting resulted in fewer and more rapid APs and more that propagated toward the cecal tip. Motor activity was well coordinated between ceca, both organs showing essentially simultaneous spike activity; 72% of APs occurred within 8.1 s of each other. No relationship between ileal and cecal activity was apparent. Prominent slow waves were recorded in the ceca (5 to 5.5/min), the same slow-wave frequency as in the ileum (small intestine). From the results obtained here and from earlier studies, we conclude that the single or brief clusters of APs represent contractions that produce mixing of the luminal contents; occasional periods of protracted APs represent evacuation of cecal contents.

Some studies have implicated the avian digestive cecae as important sites of water and solute reclamation working in concert with the lower intestine and the kidneys as part of an integrated osmoregulatory system. In Gambel's quail (Callipepla gambelii), we studied compensatory adjustments in renal function on days 6-7 and 16-17 following ligation of cecae. Plasma osmolality (Posm) varied significantly between groups with sham-operated birds (Cs), with an average (Posm) of 348 mOsm/kg H2O and quail with ligated cecae (Cx) having a (Posm) of 355 mOsm/kg H2O. We detected no change in the rate of glomerular filtration (GFR) between experimental and control groups either shortly after cecectomy or after 16-17 d following surgery. Regression analysis of GFR and urine flow rate (V) showed that Cx birds had a significantly lower V at a given GFR than did controls, evidence that Cx quail absorbed more fluid in their renal tubules. Increased fluid reabsorption was apparently driven by an enhanced reabsorption of sodium. Indeed, sodium excretion was lower in Cx quail as compared to sham-operated birds. On days 6-7, Cx quail drank more water than Cs birds, but by days 16-17 drinking rates were similar. At the end of the experiments, Cx quail showed a proliferation of microvilli along the apical membrane of the rectum, an adjustment consistent with the idea that the rectum alters its absorption capacity to adjust for the loss of cecal function.

In the digestive tract of the rock hyrax (Procavia habessinica), water is absorbed from the small intestine and from the wider part of the connecting colon running between the caecum and the colonic sac. Only little water absorption occurs from these two fermenting chambers. The outflow from the caecum is much higher than from the colonic sac mainly due to the effective absorption in the connecting colon with its very large absorptive area. A significant lower osmolality was found in the caecal contents compared with the contents in the colonic sac. The Na/K ratio was 10.7 and 1.7, respectively in these sections. Short chain fatty acids are produced at a rate of nearly 10 mmol/100 ml/hr in the contents of both the caecum and the colonic sac. The results are discussed in relation to the findings in domestic and laboratory animals.

The effect of the antioxidant N-acetyl-L-cysteine was studied in a model of polymicrobial sepsis induced in CD-1 mice by cecal ligation and puncture. N-Acetyl-L-cysteine significantly improved survival during the 6 days following sepsis induction and caused lower liver toxicity. This effect was not related to free radicals generated by xanthine oxidase which was significantly induced in liver after cecal ligation and puncture. A specific inhibitor of xanthine oxidase, allopurinol, significantly reduced this enzyme and reduced the early survival rate. The effect of N-acetyl-L-cysteine was not related either to a reduction in tumor necrosis factor production or to a modulation of nitrites or to liver glutathione content. These results show that the induction of xanthine oxidase is not deleterious in this model of sepsis and suggest that N-acetyl-L-cysteine works as a direct antioxidant and scavenger of free radicals generated from other sources.

The stomach of the rock hyrax (Procavia habessinica) is divided into a non glandular part with very slow movements, and a glandular part which rapidly mix the digesta. The large intestine has two fermentation chambers, the caecum, which rapidly mixes the digesta, and the colonic sac, which efficiently, but slowly, mixes digesta. Between these chambers runs the connecting colon. No retrograde transport is observed in any part of the large intestine.

In a canine model of the Mainz pouch, intracavitary pressure and compliance were measured during instillation of isosmotic and hyperosmotic (900 mmol/kg water) solutions of saline. Wall properties of small- and large-bowel segments of the pouch were assessed individually by sonomicrometry. Intraluminal pressures increased more steeply during filling with hyperosmotic solution, resulting in reduced distensibility of small- and large-bowel segments. Additionally, instillation of the hyperosmotic solution resulted in increased amplitudes and frequency of intracavitary pressure waves. The results indicate that this was the result of a combination of intensified bowel contractions and an increased mural tension. Topical application of oxybutynin abolished these effects. These findings are reviewed in light of the nocturnal increase in urine osmolality, its correlation with nocturnal incontinence in patients with enterocystoplasty, and possible treatment choices.

The effect of prolonged (6 h), continuous rectal distention on mouth-to-cecum and colonic transit time was studied in four unrestrained pigs. Mouth-to-cecum transit time was determined from samples of cecal efflux using the phenol red dye technique. Colonic transit time was assessed with radiopaque markers that were injected into the cecum before each trial. Rectal distention was applied 2-1/2 h before feeding, during feeding, and 3-1/2 h after feeding. No distention was applied during control conditions. Stools were collected for 48 h after marker application. Rectal distention increased mouth-to-cecum transit time (p < 0.05). Colonic transit time was also prolonged by rectal distention as shown by a significant decrease in the number of markers excreted within 36 h (p < 0.05). Rectal distention for 6 h increased colonic transit time up to 30 h following distention and prolonged mouth-to-cecum transit of a high fat liquid meal.

The effect of buspirone on corticotropin-releasing factor (CRF) and stress-stimulated cecal motility and its antagonism by 5-HT1A (spiroxatrine) and sigma (BMY 14802) antagonists were evaluated by electromyography in rats equipped with chronically implanted electrodes on the cecum and a small catheter into the right lateral ventricle of the brain. Exposure to mental stress, consisting of a fear-conditioned response, increased during 30 min the frequency of cecal spike bursts significantly (P less than 0.01). The frequency of cecal spike bursts was also increased following intracerebroventricular injection of CRF (500 ng/kg). Buspirone (1 mg/kg s.c.) abolished the stimulatory effects of mental stress and CRF on cecal motility. Whereas spiroxatrine (0.5 mg/kg s.c.) blocked the effect of buspirone on the colonic hypermotility induced by i.c.v. injection of CRF, BMY 14802 at a similar dose (0.5 mg/kg s.c.) was unable to block the action of buspirone. It is concluded that s.c. administration of buspirone suppresses the stress-induced cecal motor response through 5-HT1A receptors, probably by inhibiting the central or peripheral pathways involved in CRF mediation of these effects.

1. Amitraz was rapidly metabolised to BTS27271 after intravenous administration to sheep. 2. Amitraz and BTS27271 had significant H1-histamine antagonist activity on isolated guinea-pig ileum. BTS27271 was approximately 3.3 times as potent as amitraz. 3. Intravenous injection of amitraz and its metabolite BTS27271 caused an immediate cessation of caecal motility in sheep, which persisted for 74-245 min. 4. Caecal stasis induced by amitraz was reversed by yohimbine but only partially reversed by 2-pyridylethylamine. 5. The results suggest that despite the significant antihistamine activity of amitraz and BTS27271 in vitro, it is probably the alpha-2-adrenergic agonist activity that is the most important in causing large intestinal stasis in vivo.

Determination of CCK8- and secretin21-27-like immunoreactivity in the intestinal tract of germ-free and control mice with the modified-phage assay showed that in germ-free mice as well as in control mice the highest amount of immunoreactivity is present in extracts from the small intestines. CCK8-like immunoreactivity is about 2 times higher and secretin21-27-like immunoreactivity is about 3 times lower in an extract from the small intestines of control mice than in the comparable extract of germ-free mice. The extracts from the small intestines of germ-free and control mice were applied to a Sephadex G-50 column. Higher molecular weight CCK8- and secretin21-27-like immunoreactive material was found to be present in the extract from the small intestines of control mice and virtually absent in the extract from the small intestines of germ-free mice.

1. The effects of nicorandil on guinea-pig taenia caeci were investigated with the use of isolated smooth muscle cells and glycerin-treated muscle fiber bundles. 2. Nicorandil inhibited high K-, Ca2+- and carbachol-induced contractions in a dose-dependent manner without affecting 45Ca fluxes in isolated cells. 3. Nicorandil had no effect on ATP-induced contraction of glycerin-treated muscle fiber bundles. 4. The present results suggest that nicorandil may inhibit the contraction by action on the contractile proteins in an indirect manner in guinea-pig taenia caeci.

Electrical stimulation of the guinea-pig taenia caeci (5 Hz, 2 s) caused enhancement of the [3H]purine flux from [3H]adenosine pools, accompanied by hyperpolarization (inhibitory junction potential) and relaxation of the muscle cells (35 degrees C). Interaction with receptors sensitive to catecholamines and acetylcholine was prevented by phentolamine (10(-6)M), propranolol (10(-6)M) and atropine (10(-6)M, respectively. The hyperpolarization and relaxation were completely inhibited by tetrodotoxin (TTX; 3 X 10(-7)M) but a substantial part of the [3H]purine flux persisted. The flux from the [3H]purine pool, from the [3H]methylcholine pool and from the noradrenaline pool was enhanced in the presence of 4-aminopyridine (3 X 10(-4)M; 4-AP), known to facilitate transmitter release. The release from the [3H]methylcholine pool was limited by hemicholinium (HC-3; 5 X 10(-4) M) and the release of noradrenaline was limited by reserpine (5 mg/kg; 24 h). The excess release of [3H]purine caused by 4-AP was completely abolished in the presence of TTX in preparations treated with HC-3 and reserpine. Addition of 4-AP to the Krebs solution evoked contraction of the smooth muscle cells. This response was abolished in the presence of HC-3 or atropine. The relaxation was also observed in reserpinized preparations in the presence of HC-3 and was not inhibited by either phentolamine or propranolol but was abolished in the presence of TTX. Hyperpolarization and suppression of spike activity accompanied the relaxation induced by 4-AP in reserpinized preparations treated with HC-3. Comparable responses were evoked by electrical stimulation of taenia caeci, by adenosine triphosphate (4 X 10(-4) M; ATP) and by adenosine (4 X 10(-4) M) in these experimental conditions. These responses evoked by electrical stimulation and by ATP were reversed in the presence of apamin (3 X 10(-7) M); the effect was reflected by an increased spike activity and contraction of the muscle cells in contrast to the adenosine response.(ABSTRACT TRUNCATED AT 250 WORDS)

Forskolin (0.5-10 microM) caused hyperpolarization and relaxation of the smooth muscle cells of guinea-pig taenia caeci (35 degrees C) as measured with the sucrose-gap method. Membrane conductance, reflected by the amplitude of the electrotonic potential, was not changed during the response. The hyperpolarization could also be evoked in the absence of extracellular calcium, calcium and potassium, or calcium and sodium. Further, the 45Ca2+ efflux from taenia caeci was enhanced by forskolin. The results support the concept that calcium extrusion across the plasma membrane is promoted in the presence of forskolin by stimulation of electrogenic calcium pumping.