Involvement of 5-hydroxytryptamine 3 receptors in regulation of interdigestive gastric contractions by motilin in the dog

Itoh, Zen; Mizumoto, Akiyoshi; Iwanaga, Yuji; Yoshida, Naoyuki; Torii, Keiko U.; Wakabayashi, Keiji

doi:10.1016/0016-5085(91)90262-j

Cited by 83 publications

(44 citation statements)

References 27 publications

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“…EM523 seems to exert its action mainly by acting on the motilin receptors in the nervous system, as EM523 is a motilin receptor agonist in humans and rab bits (9). Itoh et al (11) reported that 5HT3-receptor antagonists inhibit the spontaneous and motilin-induced phase III contractions in the stomach. In this study, ICS-205-930 strongly inhibited EM523 as well as motilin-induced gas tric contractions.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Motor-Stimulating Action of EM523, an Erythromycin Derivative, and Prostaglandin F2 in Conscious Dogs

Inatomi

Satoh

et al. 1993

Japanese Journal of Pharmacology

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ABSTRACT-The effect of , an erythromycin derivative, on gastrointestinal motility was investigated using conscious dogs in the fasting state, and it was compared with those of motilin and prostaglandin F2a (PGF2a). EM523 and motilin given as i.v. infusions induced strong contractions in the stomach that migrated along the intestine. On the other hand, PGF2a stimulated intestinal contractions, but its effect on gastric motility was weak. EM523 had 1/50 the potency of motilin and 6 times the potency of PGF2a for stimulation of intestinal motility. Atropine at 0.1 mg/kg, i.v. strongly inhibited gastrointestinal contractions induced by EM523 or motilin and partly in hibited PGF2a-induced intestinal motility. ICS-205-930, a 5HT3-receptor antagonist, at a dose of 1 mg/kg, i.v. strongly inhibited EM523 or motilin-induced gastric contractions but did not affect the action of PGF2a. Infusion of EM523 at 100 ttg/kg/hr induced strong migrating contractions even when motility was depress ed by dopamine infusion or laparotomy. Infusion of PGF2a at 300 pg/kg/hr stimulated intestinal but not gastric motility under these conditions. The results of this study indicate that the cholinergic pathway and 5HT3 receptors are involved in EM523 and motilin-induced migrating gastrointestinal contractions, whereas the cholinergic pathway seems to be only partly involved in PGF2a-induced intestinal contractions.

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Section: Discussionmentioning

confidence: 99%

Comparison of the Motor-Stimulating Action of EM523, an Erythromycin Derivative, and Prostaglandin F2 in Conscious Dogs

Inatomi

Satoh

et al. 1993

Japanese Journal of Pharmacology

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“…It is known that in dog, motilin increases the motility of the stomach and small intestine by stimulating the cholinergic neurons, [3][4][5] whereas in rabbit and human it produces the contractions of the stomach, pylorus and duodenum by direct action on the smooth muscle cells. [6][7][8][9][10][11] The mechanisms of the increase in gastrointestinal (GI) motility differ with the animal species.…”

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confidence: 99%

Effects of SK-896, a New Human Motilin Analogue ([Leu13]motilin-Hse), on Postoperative Ileus in Dogs after Laparotomy.

Furuta

Takeda

Nakayama

et al. 2002

Biological & Pharmaceutical Bulletin

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The effects of SK-896, a new human motilin analogue ([Leu 13 ]motilin-Hse), on digestive tract motility in postoperative ileus were evaluated in a dog model of ileus after laparotomy. SK-896 was intravenously administered at 0.17, 0.33 and 0.67 m mg/kg starting soon after operation and then at 6-h intervals, for a total of 9 times. SK-896 progressively, dose-dependently and significantly increased the duodenal motility from 1 h after operation. The recovery time of the gastrointestinal-interdigestive migrating complex (GI-IMC) activity, which is an indicator of normal gastrointestinal tract activity after laparotomy, was 56.5؎5.0 h in the control group. SK-896 significantly shortened this recovery time. On the other hand, the plasma SK-896 concentrations declined diexponentially after administration, and can be described by a linear pharmacokinetic model within the dose range used. In addition, the pharmacokinetics of SK-896 did not change significantly at any postoperative time. There was no correlation between the plasma SK-896 concentrations and the intensity of duodenal motility, because the activity in the duodenum decreased transiently 13 h after laparotomy and increased with time thereafter. The changes in the activity are considered to reflect the progressive changes in the state of ileus. In conclusion, SK-896 increased the duodenal motility significantly, shortening the recovery time of GI-IMC-like activity in dogs with post-laparotomy ileus. Therefore, it is expected from these results that SK-896 would be useful and effective for the treatment of gastroparalysis after abdominal surgery.

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“…7-B and 8-B). These paradoxical effects of glucagon between antral and intestinal phase III contractions are similar to the antagonism of neural 5-HT3 receptors (Itoh et al, 1991). These facts indicate the involvement of cholinergic neurons and possibly 5-HT3 receptors or neurons in terms of the inhibitory effects of glucagon.…”

Section: Discussionmentioning

confidence: 68%

“…It has been commonly accepted that the cholinergic pathways and 5-HT3 neurons are involved in these contractions. (Itoh et al, 1977 ;Itoh et al, 1978 ;Itoh et al, 1991 ;Mizumoto et al, 1993 ;Haga et al, 1996). In fact, these contractions were completely inhibited by atropine sulfate and partially inhibited by hexamethonium bromide (Qin et al, 1993 ;Shiba et al, 1995).…”

Section: Discussionmentioning

confidence: 97%

Involvement of Cholinergic Motor Neurons in Pharmacological Regulation of Gastrointestinal Motility by Glucagon in Conscious Dogs.

Shimatani

1997

J. Smooth Muscle Res.

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To clarify the exact mechanisms of the pharmacological effects of glucagon on gastro intestinal motility, the following experiments were performed on the conscious and anesthe tized dogs. 1) During phase I of interdigestive migrating contractions (IMC) , glucagon (5 infusion for 5 minutes) induced phasic contractions in the duodenum , jejunum and ileum, but not in the antrum. These excitatory responses were also observed in the truncal vagotomized dogs. These contractions were abolished by atropine or hex amethonium in the conscious dogs, and also by tetrodotoxin in the anesthetized dogs . 2) Glucagon inhibited cisapride-induced contractions only in the antrum in the conscious dogs .After pre-treatment with hexamethonium, glucagon inhibited these contractions in the duodenum, jejunum and ileum as well as in the antrum. After pre-treatment with tetrodotoxin in the anesthetized dogs, glucagon did not affect acetylcholine-induced contrac tions in any region. 3) Glucagon inhibited spontaneous phase III contractions and eryth romycin-induced phase III-like contractions in the antrum, but did not inhibit either contrac tions in the other regions in the conscious dogs. These paradoxical effects of glucagon between the antrum and intestine were similar to those involved in the blockade of 5-hydroxytryptamine 3 receptors. After pre-treatment with hexamethonium , glucagon inhib ited these contractions in the duodenum, jejunum and ileum as well as in the antrum . In conclusion: 1) Glucagon latently inhibits cholinergic motor activities in the antrum and intestine not directly, by binding to either receptor on the smooth muscle cells , but through postganglionic cholinergic neurons and possibly through 5-hydroxytryptamine neurons. 2) On the other hand, in the intestine the reverse effects through preganglionic cholinergic neurons involving nicotinic and muscarinic receptors are more potent . 3) As a result, glucagon inhibits antral contractions and does not affect intestinal contractions in a con scious state.

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Involvement of 5-hydroxytryptamine 3 receptors in regulation of interdigestive gastric contractions by motilin in the dog

Cited by 83 publications

References 27 publications

Comparison of the Motor-Stimulating Action of EM523, an Erythromycin Derivative, and Prostaglandin F2 in Conscious Dogs

Comparison of the Motor-Stimulating Action of EM523, an Erythromycin Derivative, and Prostaglandin F2 in Conscious Dogs

Effects of SK-896, a New Human Motilin Analogue ([Leu13]motilin-Hse), on Postoperative Ileus in Dogs after Laparotomy.

Involvement of Cholinergic Motor Neurons in Pharmacological Regulation of Gastrointestinal Motility by Glucagon in Conscious Dogs.

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