A simplified method for assessing drug effects on gastric emptying in rats

Droppleman, David A.; Gregory, Robert L.; Alphin, R. S.

doi:10.1016/0160-5402(80)90014-5

Cited by 55 publications

(21 citation statements)

References 7 publications

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“…In contrast to bethanechol, however, metoclopramide was devoid of cholinergic side-effects, failed to enhance intestinal propulsion, did not cause diarrhea, and produced a bell-shaped dose-response curve, which is consistent with previously reported results (Droppleman et al, 1980;Purdon and Bass, 1973). These data confirm that metoclopramide acts differently from bethanechol, i.e., not via direct stimulation of muscarinic acetylcholine receptors [cf.…”

Section: Discussionsupporting

confidence: 91%

Non‐antidopaminergic, non‐cholinergic stimulation of gastric emptying with cisapride (R 51 619) in rats

Megens

Canters

Artois

et al. 1986

Drug Development Research

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Awouters: Non-antidopaminergic, non-cholinergic stimulation of gastric emptying with cisapride (R 51 619) in rats. Drug Dev. Res. 8:243-250, 1986. The gastrokinetic activity of cisapride, bethanechol, domperidone, and metoclopramide was tested in rats and compared with the direct cholinergic activity (induction of salivation and lacrimation in rats) and peripheral and central antidopamine activity (antagonism of apomorphine-induced emesis in dogs and abnormal behaviour in rats, respectively) of the compounds.Cisapride showed a high dissociation between gastrokinetic activity (0.31 mglkg) on the one hand, and direct cholinergic activity (ED50: > 40 mglkg) and peripheral and central antidopamine activity (ED50s: 3.3 and 18.6 mglkg), on the other hand. In contrast, metoclopramide combined antidopamine effects (ED50s: 0.28 and 0.76 mg/kg for peripheral and central activity) and bethanechol direct cholinergic effects (ED50s: 2.7 and 3.6 mglkg for lacrimation and salivation) with their gastrokinetic activity, which was obtained with bethanechol at 0.63 mglkg and with metoclopramide at 1.25 mglkg. Domperidone was found to be a potent and selective antagonist of peripheral dopamine receptors (ED50:0.0071 mg/kg) but failed to stimulate gastric emptying (ED50: > 10 mglkg).The present data confirm cisapride as a potent gastrokinetic compound devoid of antidopaminergic or direct cholinergic properties.

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Section: Discussionsupporting

confidence: 91%

Non‐antidopaminergic, non‐cholinergic stimulation of gastric emptying with cisapride (R 51 619) in rats

Megens

Canters

Artois

et al. 1986

Drug Development Research

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“…Gastric emptying of a semisolid meal was measured according to the method of Droppleman et al (15). The rats were fasted for 18 h before all experiments.…”

Section: Measurement Of Gastric Emptying In Ratsmentioning

confidence: 99%

“…Ninety minutes after administration of the test meal, the stomach was removed and weighed, with and without the remaining luminal content. The amount of meal emptied per rat was calculated according to the method of Droppleman et al (15).…”

Section: Measurement Of Gastric Emptying In Ratsmentioning

confidence: 99%

Anti-emetic Effect of Mosapride Citrate Hydrate, a 5-HT4 Receptor Agonist, on Selective Serotonin Reuptake Inhibitors (SSRIs)-Induced Emesis in Experimental Animals

2013

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Abstract. Although selective serotonin reuptake inhibitors (SSRIs) are widely used to treat depression, they frequently cause gastrointestinal adverse effects, such as nausea and emesis. In the present study, we investigated the anti-emetic effect of mosapride, a 5-HT 4 receptor agonist, on SSRIs-induced emesis in Suncus murinus and dogs. We also examined the effect of mosapride on SSRIs-induced delay in gastric emptying and increase in gastric vagal afferent activity in rats. Oral administration of paroxetine, but not its subcutaneous administration, dose-dependently caused emesis in both animals. Mosapride inhibited paroxetine-induced emesis in Suncus murinus and dogs with ID 50 values of 7.9 and 1.1 mg/kg, respectively. The anti-emetic effect of mosapride was partially inhibited by SB207266, a selective 5-HT 4 antagonist. Intragastric administration of paroxetine increased gastric vagal afferent discharge in anesthetized rats. Mosapride failed to suppress this increase. On the other hands, mosapride improved the delay in gastric emptying caused by paroxetine in rats. We have shown in this study that oral administration of SSRIs causes emesis and activates gastric vagal afferent activity in experimental animals and that mosapride inhibits SSRIs-induced emesis, probably via improvement of SSRIs-induced delay in gastric emptying. These findings highlight the promising potential of mosapride as an anti-emetic agent.

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“…10). The animals were fasted overnight before the experiment but were allowed free access to drinking water at all times.…”

Section: Methodsmentioning

confidence: 99%

UDP-glucose modulates gastric function through P2Y₁₄ receptor-dependent and -independent mechanisms

Bassil¹,

Bourdu²,

Townson³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Grimes AM, Hurp DP, Downham KM, Sanger GJ, Winchester WJ, Morrison AD, Moore GB. UDP-glucose modulates gastric function through P2Y 14 receptor-dependent and -independent mechanisms. Am J Physiol Gastrointest Liver Physiol 296: G923-G930, 2009. First published January 22, 2009 doi:10.1152/ajpgi.90363.2008.-P2Y receptors have been reported to modulate gastrointestinal functions. The newest family member is the nucleotide-sugar receptor P2Y 14. P2ry14 mRNA was detected throughout the rat gut, with the highest level being in the forestomach. We investigated the role of the receptor in stomach motility using cognate agonists and knockout (KO) mice. In rat isolated forestomach, 100 M UDP-glucose and 100 M UDP-galactose both increased the baseline muscle tension (BMT) by 6.2 Ϯ 0.6 and 1.6 Ϯ 0.6 mN (P Ͻ 0.05, n ϭ 3-4), respectively, and the amplitude of contractions during electrical field stimulation (EFS) by 3.7 Ϯ 1.7 and 4.3 Ϯ 2.5 mN (P Ͻ 0.05, n ϭ 3-4), respectively. In forestomach from wild-type (WT) mice, 100 M UDP-glucose increased the BMT by 1.0 Ϯ 0.1 mN (P Ͻ0.05, n ϭ 6) but this effect was lost in the KO mice (change of Ϫ0.1 Ϯ 0.1 mN, n ϭ 6). The 100 M UDP-glucose also increased the contraction amplitude during EFS in this tissue from the WT animals (0.9 Ϯ 0.4 mN, P Ͻ 0.05, n ϭ 6) but not from the KO mice (0.0 Ϯ 0.2 mN, n ϭ 6). In vivo, UDP-glucose at 2,000 mg/kg ip reduced gastric emptying in rats by 49.7% (P Ͻ 0.05, n ϭ 4 -6) and in WT and KO mice by 56.1 and 66.2%, respectively (P Ͻ 0.05, n ϭ 7-10) vs. saline-treated control animals. There was no significant difference in gastric emptying between WT and KO animals receiving either saline or D-glucose. These results demonstrate a novel function of the P2Y14 receptor associated with contractility in the rodent stomach that does not lead to altered gastric emptying after receptor deletion and an ability of UDP-glucose to delay gastric emptying without involving the P2Y14 receptor. contractility; gastric emptying PURINERGIC METABOTROPIC (P2Y) receptors regulate a number of functions in the gastrointestinal (GI) tract in response to extracellular nucleotides. These include stomach relaxation (16), smooth muscle hyperpolarization and relaxation in the colon (12), muscle contraction in the colon (21), the generation of excitatory postsynaptic potentials via P2Y 1 in submucous neurons of the ileum, and epithelial ion transport via P2Y 2 and P2Y 4 in the jejunum (13) and colon (14). The most recent addition to the P2Y family is the uridine 5Ј-diphosphate (UDP)-sugar receptor P2Y 14 (1). The four reported cognate agonists have a rank order of potency at the recombinant human, mouse, and rat receptors of UDP-glucose Ͼ UDP-galactose Ͼ UDP-glucuronic acid Ͼ UDP-N-acetylglucosamine (6, 11). UDPglucose and UDP-galactose are also less potent agonists at GPR17 (7). In terms of homology with other receptors, P2Y 14 is closest to the adenine 5Ј-diphosphate (ADP) receptors P2Y 12 and P2Y 13 with 47% amino acid identity (2). Within the seven transmembrane regions, the identity...

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A simplified method for assessing drug effects on gastric emptying in rats

Cited by 55 publications

References 7 publications

Non‐antidopaminergic, non‐cholinergic stimulation of gastric emptying with cisapride (R 51 619) in rats

Non‐antidopaminergic, non‐cholinergic stimulation of gastric emptying with cisapride (R 51 619) in rats

Anti-emetic Effect of Mosapride Citrate Hydrate, a 5-HT4 Receptor Agonist, on Selective Serotonin Reuptake Inhibitors (SSRIs)-Induced Emesis in Experimental Animals

UDP-glucose modulates gastric function through P2Y₁₄ receptor-dependent and -independent mechanisms

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A simplified method for assessing drug effects on gastric emptying in rats

Cited by 55 publications

References 7 publications

Non‐antidopaminergic, non‐cholinergic stimulation of gastric emptying with cisapride (R 51 619) in rats

Non‐antidopaminergic, non‐cholinergic stimulation of gastric emptying with cisapride (R 51 619) in rats

Anti-emetic Effect of Mosapride Citrate Hydrate, a 5-HT4 Receptor Agonist, on Selective Serotonin Reuptake Inhibitors (SSRIs)-Induced Emesis in Experimental Animals

UDP-glucose modulates gastric function through P2Y14 receptor-dependent and -independent mechanisms

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UDP-glucose modulates gastric function through P2Y₁₄ receptor-dependent and -independent mechanisms