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Introduction Methods Key Results Conclusions & Inferences The herbal preparation STW 5 ameliorates functional dyspepsia partly by relaxing smooth muscle of the proximal stomach, thus improving gastric accommodation. We explored the unknown pathways responsible for this effect by testing targets known to modulate gastric smooth muscle relaxation.STW 5‐induced relaxation of smooth muscle strips from guinea pig gastric corpus before and after pharmacological interventions were recorded with force transducers in an organ bath. ORAI1 mRNA expression was tested in the proximal stomach.Blockade of Ca2+‐activated K+ and Cl− channels, voltage‐gated L‐ or T‐type Ca2+ channels, TRPA1‐, TRPV1‐, adenosine or 5‐HT4 receptors, antagonizing ryanodine receptors, inhibiting cyclooxygenase or sarcoplasmic reticulum calcium ATPase did not affect STW 5‐evoked relaxation. Likewise, protein‐kinase A or G were not involved. However, the relaxation evoked by STW 5 was significantly reduced by phorbol‐12‐myristat‐13‐acetat, an activator of protein‐kinase C, by 2‐ aminoethyldiphenylborinate, an inhibitor of the IP3 receptor‐mediated Ca2+ release from the sarcoplasmic reticulum or by SKF‐96365, a nonselective store‐operated calcium entry (SOCE) blocker. Furthermore, the mixed TRPC3/SOCE inhibitor Pyr3, but not the selective TRPC3 blocker Pyr10, reduced the effect of STW 5. Finally, BTP2, a potent blocker of ORAI‐coupled SOCE, almost abolished STW 5‐evoked relaxation. Expression of ORAI1 could be demonstrated in the corpus/fundus.STW 5 inhibited SOCE, most likely ORAI channels, which are modulated by IP3‐ and PKC‐dependent mechanisms. Our findings impact on the design of drugs to induce muscle relaxation and help identify phytochemicals with similar modes of actions to treat gastrointestinal disturbances. [ABSTRACT FROM AUTHOR]

Abstract Background and Aim l‐Menthol has smooth muscle‐relaxing and antiperistaltic effects. We examined its effectiveness against peristalsis resumption during endoscopic submucosal dissection (ESD) of gastric tumors. Methods We retrospectively examined clinical data of 485 patients (501 lesions) who underwent ESD for upper gastrointestinal tumors in 2017. We included 119 patients (127 lesions) in whom peristaltic movement resumed during ESD and l‐menthol was applied; 366 patients (374 lesions) without l‐menthol application were used as controls. Video recordings were reviewed to determine whether l‐menthol suppressed peristalsis resumption. Results In cases with l‐menthol application, 2 (2.9%), 36 (14.3%), and 89 (71.2%) lesions were found in the upper (U), middle (M), and lower (L) regions, respectively. In the control group, the corresponding values were 66 (17.6%), 215 (57.5%), and 93 (24.9%), respectively. l‐Menthol efficacy was observed in 116 of the 127 treated lesions (91.3%), over 90% of which were in the posterior wall of the U region, anterior wall and greater curvature of the M region, and anterior wall and lesser curvature of the L region. The most and least effective areas for l‐menthol application were the anterior wall of gastric antrum and posterior wall of the M region, respectively. The mean time from application to peristalsis inhibition was 8.7 s. No adverse effects were observed; perforation and secondary hemorrhage were not significantly different between the groups. Conclusion Direct l‐menthol application to the submucosal layer during mucosal resection affects smooth muscles and rapidly inhibits peristalsis resumption. Clinically, l‐Menthol can be used to suppress peristalsis recurrence during ESD, without adverse effects.

Background and Aim: l‐Menthol has smooth muscle‐relaxing and antiperistaltic effects. We examined its effectiveness against peristalsis resumption during endoscopic submucosal dissection (ESD) of gastric tumors. Methods: We retrospectively examined clinical data of 485 patients (501 lesions) who underwent ESD for upper gastrointestinal tumors in 2017. We included 119 patients (127 lesions) in whom peristaltic movement resumed during ESD and l‐menthol was applied; 366 patients (374 lesions) without l‐menthol application were used as controls. Video recordings were reviewed to determine whether l‐menthol suppressed peristalsis resumption. Results: In cases with l‐menthol application, 2 (2.9%), 36 (14.3%), and 89 (71.2%) lesions were found in the upper (U), middle (M), and lower (L) regions, respectively. In the control group, the corresponding values were 66 (17.6%), 215 (57.5%), and 93 (24.9%), respectively. l‐Menthol efficacy was observed in 116 of the 127 treated lesions (91.3%), over 90% of which were in the posterior wall of the U region, anterior wall and greater curvature of the M region, and anterior wall and lesser curvature of the L region. The most and least effective areas for l‐menthol application were the anterior wall of gastric antrum and posterior wall of the M region, respectively. The mean time from application to peristalsis inhibition was 8.7 s. No adverse effects were observed; perforation and secondary hemorrhage were not significantly different between the groups. Conclusion: Direct l‐menthol application to the submucosal layer during mucosal resection affects smooth muscles and rapidly inhibits peristalsis resumption. Clinically, l‐Menthol can be used to suppress peristalsis recurrence during ESD, without adverse effects. [ABSTRACT FROM AUTHOR]

Background Rikkunshito ( RKT) is a gastroprotective herbal medicine. In this study, we investigated the role of RKT in the relaxation of the gastric body (fundus and corpus) and antrum. Methods We used Suncus murinus, a unique small model animal with similar gastrointestinal motility to humans and dogs. RKT was added at 0.1, 1.0, and 5.0 mg/mL to induce relaxation in vitro; the outcome measure was the intensity of relaxation. The number of spontaneous antral contractions in the absence or the presence of RKT was also counted. Key Results Rikkunshito induced the relaxation of the gastric body and antrum and decreased the number of spontaneous antral contractions in a dose-dependent manner. The responses to RKT (1.0 mg/mL) were not affected by pretreatment with atropine, N-nitro- l-arginine methyl ester, ritanserin, or ondansetron. On the other hand, timolol almost completely reversed the relaxation induced by RKT (1.0 mg/mL) on the gastric body and antrum and the occurrence of the spontaneous antral contractions. Both butoxamine, a β2-adrenoreceptor antagonist, and L 748337, a β3-adrenoreceptor antagonist, but not CGP 20712, a β1-adrenoreceptor antagonist, significantly reversed the RKT-induced (1.0 mg/mL) gastric relaxation. Conclusions & Inferences These results indicate that RKT stimulates and modulates gastric relaxation through β2- and β3-adrenergic, but not β1-adrenergic, pathways in S. murinus. [ABSTRACT FROM AUTHOR]

We have previously demonstrated that menthol reduces murine gastric tone in part through a neural mechanism, involving adrenergic pathways and reduction of ongoing release of acetylcholine from enteric nerves. In the present study we aimed to verify whether the gastric relaxation to menthol may be triggered by interaction with neural receptors or ionic channels proteins, such as transient receptor potential (TRP)-melastatin8 (TRPM8), TRP-ankyrin 1 (TRPA1), 5-hydroxytriptamine 3 (5-HT 3 ) receptor or cholinergic nicotinic receptors. Spontaneous mechanical activity was detected in vitro as changes in intraluminal pressure from isolated mouse stomach. Menthol (0.3−30 mM) induced gastric relaxation which was not affected by 5-benzyloxytryptamine, a TRPM8 receptor antagonist, HC030031, a TRPA1 channel blocker. In addition, allylisothiocyanate, a TRPA1 agonist, but not (2S,5R)-2-Isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexanecarboximide, a selective TRPM8 agonist, induced gastric relaxation. Genic expression of TRPA1, but not of TRPM8, was revealed in mouse stomach. Indeed, menthol-induced gastric relaxation was significantly reduced by hexamethonium, cholinergic nicotinic receptor antagonist. Menthol, at concentrations that failed to affect gastric tone, reduced the contraction induced by dimethylphenylpiperazinium, nicotinic receptor agonist. The joint application of hexamethonium and atropine, muscarinc receptor antagonist, or hexamethonium and phentholamine, α-adrenergic receptor antagonist, did not produce any additive reduction of the relaxant response to menthol. Lastly, ondansetron, a 5-HT 3 receptor antagonist, was ineffective. In conclusion, our study suggests that nicotinic receptors, but not TRP and 5-HT 3 receptors, are molecular targets for menthol inducing murine gastric relaxation, ultimately due to the reduction of acetylcholine release from enteric nerves. [ABSTRACT FROM AUTHOR]

Background: The topical antispasmodic agent l-menthol is useful for inhibiting gastric peristalsis during diagnostic upper gastrointestinal endoscopy. However, it remains unclear whether l-menthol is similarly effective during therapeutic endoscopy, thereby improving treatment outcomes in a clinical setting. Methods: A total of 83 patients scheduled to undergo endoscopic treatment at 8 Japanese referral centers were randomly assigned to receive l-menthol or placebo. The degree of gastric peristalsis (peristaltic score: grade 1-5) was assessed by an independent committee. The primary outcome was the proportion of subjects in whom no or mild peristalsis (grade 1 or 2) was maintained throughout endoscopic treatment. Secondary outcomes were the duration of sustained response and the incidence of adverse drug reactions. Results: The proportion of patients with no or mild peristalsis was significantly higher in the l-menthol group (85.4 %, 95 % confidence intervals 70.8-94.4: 35/41 subjects) than in the placebo group (39.0 %, 24.2-55: 16/41; P < 0.001). The sustained response rates in the l-menthol and the placebo were, respectively, 90.0 and 39.6 % 30 min post-dose, and 79.9 and 35.7 % at the completion of the resection. The sustained response rates were significantly higher in the l-menthol group than in the placebo group ( P < 0.001, log-rank test). The incidence of adverse drug reactions did not differ significantly between the two groups ( P = 1.000). Conclusions: During gastric endoscopic submucosal dissection, spraying l-menthol on the gastric mucosa significantly suppressed peristalsis, with minimal adverse drug reactions as compared with placebo. l-menthol solution might be useful for therapeutic endoscopy. [ABSTRACT FROM AUTHOR]

The inhibitory action of hyperglycemia is mediated by vagal afferent fibers innervating the stomach and duodenum. Our in vitro studies showed that a subset of nodose ganglia neurons is excited by rising ambient glucose, involving inactivation of ATP-sensitive K+ (KATP) channels and leading to membrane depolarization and neuronal firing. To investigate whether nodose ganglia KATP channels mediate gastric relaxation induced by hyperglycemia, we performed in vivo gastric motility studies to examine the effects of KATP channel activators and inactivators. Intravenous infusion of 20% dextrose induced gastric relaxation in a dose-dependent manner. This inhibitory effect of hyperglycemia was blocked by diazoxide, a KATP channel activator. Conversely, tolbutamide, a KATP channel inactivator, induced dose-dependent gastric relaxation, an effect similar to hyperglycemia. Vagotomy, perivagal capsaicin treatment, and hexamethonium each prevented the inhibitory action of tolbutamide. Similarly, NG-nitro-l-arginine methyl ester, an inhibitor of nitric oxide synthase, also blocked tolbutamide's inhibitory effect. To show that KATP channel inactivation at the level of the nodose ganglia induces gastric relaxation, we performed electroporation of the nodose ganglia with small interfering RNA of Kir6.2 (a subunit of KATP) and plasmid pEGFP-N1 carrying the green fluorescent protein gene. The gastric responses to hyperglycemia and tolbutamide were not observed in rats with Kir6.2 small interfering RNA-treated nodose ganglia. However, these rats responded to secretin, which acts via the vagal afferent pathway, independently of KATP channels. These studies provide in vivo evidence that hyperglycemia induces gastric relaxation via the vagal afferent pathway. This action is mediated through inactivation of nodose ganglia KATP channels. [ABSTRACT FROM AUTHOR]

Background: Functional dyspepsia (FD) is a heterogeneous disease characterized by various upper abdominal symptoms. The major mechanism of FD symptoms includes impaired fundic accommodation, delayed gastric emptying, and visceral hypersensitivity. We developed a novel drinking-ultrasonography test to combine a drink test with ultrasonography to assess gastric motility and sensory function of FD patients. Method: Subjects were 60 successive FD patients according to the Rome III criteria. A drinking-ultrasonography test was performed after subjects had fasted. The subjects ingested 200 ml of water at 2-min intervals 4 times (total 800 ml) through a straw. The maximum cross section of the proximal stomach was visualized before water intake, after each water intake, and 5 and 10 min after the completion of drinking using extracorporeal ultrasonography. Abdominal symptoms were evaluated using the visual analog scale (VAS) a total of 5 times. The normal range of cross-sectional area and VAS were set using average ± standard deviations of 33 healthy volunteers. Cases outside the normal range were diagnosed with a motor or sensory disorder. Results: The drinking-ultrasonography test classified FD patients into four groups without adverse effect or trouble. The distribution of each group was 27% in the normal group, 15% in the impaired relaxation group, 10% in the delayed emptying group, and 48% in the visceral hypersensitivity group. There was no significant correlation between the pathophysiological classification and subtypes of FD defined by the Rome III criteria. Conclusion: We developed a novel drinking-ultrasonography test that was effective in classifying FD patients according to pathophysiological features. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Flavonoids are a large heterogeneous group of benzo-gamma-pyrone derivatives, which are abundantly present in our diet. In this study we investigated the effects of six flavonoids (apigenin, genistein, quercetin, rutin, naringenin and catechin) on the gastric tone in mouse isolated stomach. The mechanical activity was recorded as changes of intraluminal pressure. All flavonoids tested produced a concentration-dependent relaxation, which was reversible after washout. The relative order of potency of the flavonoids was apigenin≥genistein>quercetin>naringenin≥rutin>catechin. Analysis of the chemical structure showed that the relaxant activity was progressively diminished by the presence of hydroxyl group at C-3, saturation of the C-2, C-3 double bound, saturation of the C-2, C-3 double bound coupled with lack of the C-4 carbonyl and glycosylation. The flavonoid-induced relaxations were not modified in the presence of tetrodotoxin, a voltage-dependent Na+-channel blocker, Nω-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, indomethacin, an inhibitor of cycloxygenase or tetraethylammonium, a non-selective blocker of potassium channels. In conclusion, this study provides the first experimental evidence for gastric relaxant activity of flavonoids. This action is influenced to a great extent by the structure of the molecules and it seems not to be dependent on neural action potentials, NO/prostaglandin production or activation of K+ channels. [Copyright &y& Elsevier]

Abstract: A definitive role for chromogranin A (CGA)-derived fragments in the control of the gastrointestinal smooth muscle contractility has not been yet established. The purpose of the present study was to evaluate, in vitro, the effects of the recombinant vasostatin 1–78 (VS-1), CGA 7–57 and CGA 47–66 on the mouse gastric mechanical activity, recording the changes of intraluminal pressure. VS-1, CGA 7–57 and CGA 47–66 produced concentration-dependent relaxations. Mouse anti-vasostatin-1 monoclonal antibody 5A8, recognising the region 53–57, abolished the relaxation induced by VS-1, indicating the specificity of the effect. The relaxation was significantly reduced by tetrodotoxin (TTX), blocker of neuronal voltage-dependent Na+ channels, l-NAME, inhibitor of nitric oxide (NO) synthase, or apamin, blocker of small conductance Ca2+-dependent K+ channels. The joint application of TTX and l-NAME did not show any additive effects, whereas TTX plus apamin abolished the VS-1 response. The results suggest that the N-terminal CGA-derived peptides are able to relax mouse gastric muscle and, therefore, they point out an inhibitory role of vasostatin I in the gastrointestinal tract. The relaxation is mediated in part by neural mechanisms through NO production and in part by non-neural mechanisms involving the opening of small conductance Ca2+-dependent K+ channels. [Copyright &y& Elsevier]

Abstract: Obestatin is a new peptide for which anorexigenic effects were recently reported in mice. We investigate whether peripheral injection of obestatin or co-injection with cholecystokinin (CCK) can modulate food intake, gastric motor function (intragastric pressure and emptying) and gastric vagal afferent activity in rodents. Obestatin (30, 100 and 300μg/kg, i.p.) did not influence cumulative food intake for the 2h post-injection in rats or mice nor gastric emptying in rats. In rats, obestatin (300μg/kg) did not modify CCK (1μg/kg, i.p.)-induced significant decrease in food intake (36.6%) and gastric emptying (31.0%). Furthermore, while rats injected with CCK (0.3μg/kg, i.v.) displayed gastric relaxation, no change in gastric intraluminal pressure was elicited by obestatin (300μg/kg, i.v.) pre- or post-CCK administration. In in vitro rat gastric vagal afferent preparations, 20units that had non-significant changes in basal activity after obestatin at 30μg responded to CCK at 10ng by a 182% increase. These data show that obestatin neither influences cumulative food intake, gastric motility or vagal afferent activity nor CCK-induced satiety signaling [Copyright &y& Elsevier]

Abstract: The aim of this study was to investigate the location of photodegradable nitric oxide (NO) store using a pharmacological approach in mouse gastric fundus. The ultraviolet light irradiation (UV; 360 nm, 60 s), electrical field stimulation (EFS; 4 Hz, 25 V, 1 ms, 15s-train), exogenous nitric oxide (NO; 10 μM), nitroglycerin (100 μM) and isoproterenol (5 nM) induced relaxation in mouse gastric fundus preparations in the absence or presence of an intact mucosa. The NO scavenger, haemoglobin (20 μM), significantly inhibited the relaxation of intact and denuded mucosa stomach fundus to UV light irradiation, EFS and NO, but not to nitroglycerin and isoproterenol. The superoxide anion generator, pyrogallol (50 μM), inhibited relaxation of intact and denuded mucosa stomach fundus induced by UV light irradiation, EFS, NO, but not to nitroglycerin and isoproterenol. The inhibition observed with pyrogallol was prevented by exogenous Cu/Zn superoxide dismutase (SOD; 100 U/ml), a membrane impermeable antioxidant. The Cu/Zn SOD inhibitor, diethyldithiocarbamic acid (DETCA; 8 mM), inhibited the relaxation of intact and denuded mucosa stomach fundus to UV light irradiation, EFS, NO and nitroglycerin but not those to isoproterenol. Exogenous SOD (100 U/ml) partially prevented the inhibitory effect of DETCA on relaxation to UV light irradiation, EFS, NO but not to nitroglycerin. DETCA-induced inhibition of the nitroglycerin-induced relaxation was partially prevented by the cell-permeable polyethylene-glycol–superoxide dismutase (100 U/ml). These results indicate that photodegradable NO store is, at least in part, unlikely to be within smooth muscle cells, and furthermore, that UV light-induced relaxation is not dependent on gastric mucosal layer. [Copyright &y& Elsevier]

Alterations of gastric mechanical activity have been reported in mdx mouse, animal model for Duchenne muscular dystrophy. This study examined if alterations in the vasoactive intestinal polypeptide (VIP) system are present in mdx stomach. Gastric mechanical activity was recorded in vitro as changes of endoluminal pressure and neurally or pharmacologically evoked relaxations were analysed in mdx vs normal stomach. Reverse-transcription polymerase chain reaction was used to detect inducible nitric oxide synthase (iNOS) expression. Relaxations to sodium nitroprusside in mdx stomach showed no difference in comparison with normal preparations. In normal stomach, VIP produced relaxation, which was reduced by VIP6-28, antagonist of VIP receptors, but was not modified by N ω-nitro-l-arginine methyl ester (l-NAME), 1-H-oxodiazol-[1,2,4]-[4,3-a]quinoxaline-1-one (ODQ) or by N-(3-(aminomethyl)-benzyl)acetamidine (1400W) and aminoguanidine, inhibitors of iNOS. In contrast, in mdx stomach VIP responses were antagonized not only by VIP6-28, but also byl-NAME, ODQ, 1400W or aminoguanidine. In normal stomach, the slow relaxation evoked by stimulation at high frequency was reduced by VIP6-28, but it was unaffected by 1400W or aminoguanidine. In mdx stomach, it was reduced by VIP6-28 or 1400W, which did not show additive effects. iNOS mRNA was expressed only in mdx stomach. The results suggest that in mdx gastric preparations, iNOS is functionally expressed, being involved in the slow relaxation induced by VIP. [ABSTRACT FROM AUTHOR]

The aim of the present study was to examine the role of NK1 and NK2 receptors in the control of mechanical activity of mouse stomach. In this view, the motor effects induced by NK1 and NK2 receptor agonists and antagonists were analyzed, measuring motility as intraluminal pressure changes in mouse-isolated stomach preparations. In parallel, immunohistochemical studies were performed to identify the location of NK1 and NK2 receptors on myenteric neurons and smooth muscle cells.Substance P (SP) induced biphasic effects: a contraction followed by relaxation; neurokinin A (NKA) and [β-Ala8]-NKA(4−10), selective agonist of NK2 receptors, evoked concentration-dependent contractions, whereas [Sar9, Met(O2)11]-SP, selective agonist of NK1 receptors, induced concentration-dependent relaxation.SR48968, NK2 receptor antagonist, did not modify the spontaneous activity and reduced the contractile effects induced by tachykinins without affecting the relaxation. SR140333, NK1 receptor antagonist, did not modify the spontaneous activity and antagonized the relaxant response to tachykinins, failing to affect the contractile effects.The relaxation to SP or to [Sar9, Met(O2)11]-SP was abolished by tetrodotoxin (TTX) and significantly reduced by Nω-nitro-L-arginine methyl ester (L-NAME).NK2-immunoreactivity (NK2-IR) was seen at the level of the smooth muscle cells of both circular and longitudinal muscle layers. NK1-immunoreactive (NK1-IR) neurons were seen in the myenteric ganglia and NK1/nNOS double labeling revealed that some neurons were both NK1-IR and nNOS-IR.These results suggest that, in mouse stomach, NK1 receptors, causing relaxant responses, are present on nitrergic inhibitory myenteric neurons, whereas NK2 receptors, mediating contractile responses, are present at muscular level.British Journal of Pharmacology (2006) 147, 430–436. doi:10.1038/sj.bjp.0706645; published online 9 January 2006 [ABSTRACT FROM AUTHOR]

Despite gastric feeding being a common method of artificial nutritional support, little is known about the effects of enteral nutrition on fundic motor function. The objective of this study was to assess variations of fundic tone and their relation to antroduodenal motility before, during and after nasogastric feeding supplemented or not with fibers.Double-blinded studies were performed in random order with the three different diets (2100 kJ) in eight volunteers: fiber free (FF), insoluble fiber (IF) or mixed fiber (MF). Fundic tone was recorded by barostat concomitantly with antroduodenal manometry.Before the infusion, seven spontaneous fundic relaxations occurred during the 24 studies. Concomitantly or less than 2 min before these relaxations, phase III of the migrating motor complex (MMC) with a duodenal onset was recorded. Only the 17 studies without spontaneous fundic relaxation (4 FF, 6 MF, 7 IF) were suitable for the assessment of fundic response to infusion. Disappearance of the volume waves at the beginning and during the whole infusion was observed in 11/17 studies (FF 50%, MF 66% and IF 71%, NS), but a proximal gastric relaxation following the beginning of the infusion occurred in only three individuals, one with the FF and two with IF. When it occurred, fundic relaxation was observed within 2 min and was not different from those observed spontaneously.Gastric infusion of a polymeric diet, supplemented or not with fiber, did not promote fundic relaxation in most of the cases but often induced a disappearance of gastric volume waves. [ABSTRACT FROM AUTHOR]

1 Accumulating data have been published emphasizing the important role 5-hydroxytryptamine (5-HT) receptors in proximal stomach relaxation. However, a proper in vivo characterization of 5-HT receptors mediating gastric relaxation is still missing. In the current study, we focus on the in vivo characterization of 5-HT I[SUB(A)], receptors mediating relaxation of the proximal stomach in conscious dogs.2 Beagle dogs were equipped with a gastric fistula. In the conscious slate, volume changes within an intragastric bag were measured at constant pressure by means of a barostat. Results are presented as the maximum volume increase after treatment (mean ± s.e.m.). All drugs were injected intravenously.3 The 5-HTI[SUB1(A)], receptor agonist flesinoxan (10, 50, 100 and 150 μg kg[sup-1]) induced a dose-dependent relaxation of the canine proximal stomach (5()± 10, 2.30)± 51, 290±.38 and 275±33ml, respectively: n = 9-ll). The selective 5-HTI[SUB1(A)], receptor antagonist WAY-100635 dose-dependently inhibited the flesinoxan-induced relaxation. N[SUPG]-nitro-L-arginine methyl ester did not affect this relaxation, suggesting that nitrergic nerves are not involved.4 After supradiaphragmatic vagotomy, the baseline of the intragastric volume was larger compared to that before vagotomy (317±50 vs I42±28ml. respectively: n=5). Compensation for (his by either reduction of the intraballoon pressure re or infusion of a contractile dose of bethanechol did not establish a condition in which flesinoxan was able to relax the stomach. In contrast, nitroprusside induced a significant gastric relaxation when tone was increased by bethanechol.5 It is concluded that flesinoxan induces proximal gastric relaxation in conscious dogs via 5-HTI[SUB1(A)] receptors. The response is mediated through a vagal pathway without involvement of nitrergic nerves. [ABSTRACT FROM AUTHOR]

: BackgroundBecause the stomach plays an important role in the development of satiety, gastric function was examined in bulimia nervosa (BN).: MethodsSixteen patients with BN and 16 controls swallowed an inflatable bag, which was positioned in the proximal stomach. Minimal distending pressure (MDP), the pressure needed to overcome intraabdominal pressure, was determined. Gastric volume was recorded after subjects drank a liquid meal.: ResultsMDP was similar in patient and control groups (7.56 ± 2.13 vs. 7.13 ± 2.06 mmHg; t = .57, df = 30, p = .58). Average postmeal gastric relaxation was significantly lower in the patient group (29.7 ± 97.8 vs. 105.1 ± 103.3 mL; t = 2.13, df = 30, p = .042).: ConclusionsStomach relaxation following food consumption is significantly diminished in patients with BN. Physiologic abnormalities of stomach function in BN may contribute to the perpetuation of disturbances in behavior in this disorder. [Copyright &y& Elsevier]

1 The neurotransmitters involved in NANC relaxation and their possible interactions were investigated in mouse isolated stomach, recording the motor responses as changes of endoluminal pressure from whole organ. 2 Field stimulation produced tetrodotoxin-sensitive, frequency-dependent, hiphasic responses: rapid transient relaxation followed by a delayed inhibitory component. 3 The inhibitor of the synthesis of nitric oxide (NO), L -NAME. abolished the rapid relaxation and significantly reduced the slow relaxation. Apamin, blocker of Ca[sup2+] -dependent K[sup+] channels, or ADPβS, which desensitises P[sub2x] purinoceptors, reduced the slow relaxation to 2[mdash]8HZ, without affecting that to 16 [mdash] 32 Hz or the last relaxation. α-Chymotrypsin or vasoactive intestinal polypeptide 6[mdash]28(VIP6[mdash]28). antagonist of VIP receptors, failed to affect the fast component or the delayed relaxation to 2[mdash]4Hz. but antagonised the slow component to 8[mdash]32Hz. 4 Relaxation to sodium nitroprisside was not affected by L-NAME, apamin or ADPβS, but was reduced by α-chymotrypsin or VIP6—28. Relaxation to VIP was abolished by &alpha-chymotrypsin, antagonised by V1P6—28, but was not affected by L-NAME, apamin or ADPβS- Relaxation to ATP was abolished by apamin, antagonised by ADP&betaS. hut was not affected by L-NAME or α-chymotrypsin. 5 The present results suggest that NO is responsible for the rapid relaxation and partly for the slow relaxation. AT P is involved in the slow relaxation evoked by low frequencies of stimulation. VIP is responsible for the slow relaxation evoked by high frequencies of stimulation. The different neurotransmitters appear to work in parallel, although NO could serve also as a neuromodulator that facilitates release of VIP. [ABSTRACT FROM AUTHOR]

Abstract Gastric electrical stimulation (GES) improves symptoms in patients with gastroparesis. However, the underlying mechanisms remain unclear. To determine if GES at proximal and distal stomach could affect the biomechanical properties of the stomach, thus contributing to the beneficial effect of GES. Four pairs of electrodes were implanted along the greater curvature of the stomach in seven dogs. Gastric tone and compliance was assessed with a barostat. Measurements were obtained randomly during control and proximal and distal stimulation (4 mA, 375 ms and 6/18 cpm). Data as mean or median (25–75th percentiles). Gastric compliance was not affected by proximal and distal GES. Gastric tone was significantly reduced during proximal GES: 82.0 (66.8, 89.1) mL vs control 49.7 (39.6,75.9) mL at 6 cpm (P = 0.016), and 90.6 (54.5, 117.9) mL vs control 62.8 (39.6, 75.9) mL at 18 cpm (P = 0.031). Tone was not affected by distal GES at 6 cpm: 95.8 (46.3, 106.7) mL vs control 75.2 (49.7, 86.1) mL (P = 0.47) and at 18 cpm: 80.4 (38.1, 170.3) mL vs control 62.8 (44.6, 156.3) mL (P = 0.44). Proximal GES induces gastric relaxation. This effect, if seen also in humans, may explain, in part, the symptomatic improvement associated with GES therapy in patients with gastroparesis. [ABSTRACT FROM AUTHOR]

Secretin has been shown to delay gastric emptying and inhibit gastric motility. We have demonstrated that secretin acts on the afferent vagal pathway to induce gastric relaxation in the rat. However, the efferent pathway that mediates the action of secretin on gastric motility remains unknown. We recorded the response of intragastric pressure to graded doses of secretin administered intravenously to anaesthetized rats using a balloon attached to a catheter and placed in the body of the stomach. Secretin evoked a dose-dependent decrease in intragastric pressure. The threshold dose of secretin was 1.4 pmol kg−1 h−1 and the effective dose, 50% was 5.6 pmol kg−1 h−1. Pretreatment with hexamethonium markedly reduced gastric relaxation induced by secretin (5.6 pmol kg−1 h−1). Bilateral vagotomy also significantly reduced gastric motor responses to secretin. Administration of NG-nitro-l-arginine methyl ester (10 mg kg−1) did not affect gastric relaxation induced by secretin. In contrast, intravenous administration of a vasoactive intestinal polypeptide (VIP) antagonist (30 nmol kg−1) reduced the gastric relaxation response to secretin (5.6 pmol kg−1 h−1) by 89 ± 5%. Indomethacin (2 mg kg−1) reduced gastric relaxation induced by secretin (5.6 pmol kg−1 h−1) by 87 ± 5%. Administration of prostaglandin (48 mg kg−1 h−1) prevented this inhibitory effect. Indomethacin also reduced gastric relaxation induced by VIP (300 pmol kg−1) by 90 ± 7%. These observations indicate that secretin acts through stimulation of presynaptic cholinergic neurons in a vagally mediated pathway. Through nicotinic synapses, secretin stimulates VIP release from postganglionic neurons in the gastric myenteric plexus, which in turn induces gastric relaxation through a prostaglandin-dependent pathway. [ABSTRACT FROM AUTHOR]