Oral administration of MA-2029, a novel selective and competitive motilin receptor antagonist, inhibits motilin-induced intestinal contractions and visceral pain in rabbits

Sudo, Hirokazu; Yoshida, Shoshin; Muramatsu, Hiroyasu; Onoma, Mitsu; Kamei, Koji; Cynshi, Osamu; Kuromaru, Osamu; Peeters, Theo; Takanashi, Hisanori

doi:10.1016/j.ejphar.2007.11.049

Cited by 21 publications

(12 citation statements)

References 34 publications

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“…Some previous studies have revealed that an increase in plasma motilin concentration results in simultaneous contractile activity in the stomach (Itoh et al 1978;Janssens et al 1983). Also, exogenous motilin administration induced MMC phase III-like contraction in the stomach (Itoh et al 1976) and gastric phase III contraction was completely eliminated by neutralizing circulating motilin with motilin antiserum or motilin antagonist (Lee et al 1983(Lee et al , 1978Ozaki et al 2009;Sudo et al 2008), indicating that endogenous motilin induces gastric phase III in the interdigestive period. However, these rhythmic motor patterns originate from the foregut and propagate downward in the alimentary canal (Kellow et al 1986;Sanger et al 2010).…”

Section: Introductionmentioning

confidence: 93%

The proximal gastric corpus is the most responsive site of motilin-induced contractions in the stomach of the Asian house shrew

et al. 2016

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The migrating motor complex (MMC) is responsible for emptying the stomach during the interdigestive period, in preparation for the next meal. It is known that gastric phase III of MMC starts from the proximal stomach and propagates the contraction downwards. We hypothesized that a certain region of the stomach must be more responsive to motilin than others, and that motilin-induced strong gastric contractions propagate from that site. Stomachs of the Suncus or Asian house shrew, a small insectivorous mammal, were dissected and the fundus, proximal corpus, distal corpus, and antrum were examined to study the effect of motilin using an organ bath experiment. Motilin-induced contractions differed in different parts of the stomach. Only the proximal corpus induced gastric contraction even at motilin 10(-10) M, and strong contraction was induced by motilin 10(-9) M in all parts of the stomach. The GPR38 mRNA expression was also higher in the proximal corpus than in the other sections, and the lowest expression was observed in the antrum. GPR38 mRNA expression varied with low expression in the mucosal layer and high expression in the muscle layer. Additionally, motilin-induced contractions in each dissected part of the stomach were inhibited by tetrodotoxin and atropine pretreatment. These results suggest that motilin reactivity is not consistent throughout the stomach, and an area of the proximal corpus including the cardia is the most sensitive to motilin.

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Section: Introductionmentioning

confidence: 93%

The proximal gastric corpus is the most responsive site of motilin-induced contractions in the stomach of the Asian house shrew

et al. 2016

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“…Motilin, a fascinating hormone for the physiologist, is a gastrointestinal (GI) hormone with 22 amino acid residues 1 and is thought to be an important peptide involved in the control of interdigestive contractile activity in the gastrointestine of several animals including humans and dogs. Many researchers have shown that an increase in plasma motilin concentration caused simultaneous contractile activity in the stomach, 2,3 that phase III contractions in the stomach were induced by exogenous motilin administration, 4 and that spontaneous gastric phase III contractions were completely eliminated by neutralizing circulating motilin with motilin antiserum or motilin antagonist, 5–7 indicating endogenous motilin stimulates gastric phase III contraction in the interdigestive motor complex.…”

Section: Introductionmentioning

confidence: 99%

Myenteric neural network activated by motilin in the stomach of Suncus murinus (house musk shrew)

Mondal

Kawamoto

Yanaka

et al. 2011

Neurogastroenterology &Amp; Motility

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“…Oral dosing of the motilin receptor antagonist MA-2029 to rabbits reduced motilin-induced colonic contractions (Sudo et al, 2008). MA-2029 also reduced abdominal muscle contractions induced by administration of motilin in combination with colorectal distension, indicating a reduction in the visceral pain experienced by these animals that had been exacerbated by motilin (Sudo et al, 2008). Similarly, MA-2029 inhibited motilin-induced increases in gastric fundus tone, GI transit, and diarrhea in conscious dogs without effects on basal GI tone or motility (Ozaki et al, 2009).…”

Section: Translation To Drugsmentioning

confidence: 99%

The Hungry Stomach: Physiology, Disease, and Drug Development Opportunities

Sanger¹,

Hellström²,

Näslund³

2011

Front. Pharmacol.

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During hunger, a series of high-amplitude contractions of the stomach and small intestine (phase III), which form part of a cycle of quiescence and contractions (known as the migrating motor complex, MMC), play a “housekeeping” role prior to the next meal, and may contribute toward the development of hunger. Several gastrointestinal (GI) hormones are associated with phase III MMC activity, but currently the most prominent is motilin, thought to at least partly mediate phase III contractions of the gastric MMC. Additional GI endocrine and neuronal systems play even more powerful roles in the development of hunger. In particular, the ghrelin-precursor gene is proving to have a complex physiology, giving rise to three different products: ghrelin itself, which is formed from a post-translational modification of des-acyl-ghrelin, and obestatin. The receptors acted on by des-acyl-ghrelin and by obestatin are currently unknown but both these peptides seem able to exert actions which oppose that of ghrelin, either indirectly or directly. An increased understanding of the actions of these peptides is helping to unravel a number of different eating disorders and providing opportunities for the discovery of new drugs to regulate dysfunctional gastric behaviors and appetite. To date, ghrelin and motilin receptor agonists and antagonists have been described. The most advanced are compounds which activate the ghrelin and motilin receptors which are being progressed for disorders associated with gastric hypomotility.

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Oral administration of MA-2029, a novel selective and competitive motilin receptor antagonist, inhibits motilin-induced intestinal contractions and visceral pain in rabbits

Cited by 21 publications

References 34 publications

The proximal gastric corpus is the most responsive site of motilin-induced contractions in the stomach of the Asian house shrew

The proximal gastric corpus is the most responsive site of motilin-induced contractions in the stomach of the Asian house shrew

Myenteric neural network activated by motilin in the stomach of Suncus murinus (house musk shrew)

The Hungry Stomach: Physiology, Disease, and Drug Development Opportunities

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