Physiological characteristics of gastric contractions and circadian gastric motility in the free-moving conscious house musk shrew (Suncus murinus). Am J Physiol Regul Integr Comp Physiol 299: R1106 -R1113, 2010. First published August 4, 2010 doi:10.1152/ajpregu.00278.2010.-Although many studies have demonstrated the physiological action of motilin on the migrating motor complex, the precise mechanisms remain obscure. To obtain new insights into the mechanisms, we focused on the house musk shrew (Suncus murinus, suncus used as a laboratory name) as a small model animal for in vivo motilin study, and we studied the physiological characteristics of suncus gastrointestinal motility. Strain gauge transducers were implanted on the serosa of the gastric body and duodenum, and we recorded gastrointestinal contractions in the free-moving conscious suncus and also examined the effects of intravenous infusion of various agents on gastrointestinal motility. During the fasted state, the suncus stomach and duodenum showed clear migrating phase III contractions (intervals of 80 -150 min) as found in humans and dogs. Motilin (bolus injection, 100-300 ng/kg; continuous infusion, 10-100 ng · kg Ϫ1 · min Ϫ1 ) and erythromycin (80 g·kg Ϫ1 · min Ϫ1 ) induced gastric phase III contractions, and motilin injection also increased the gastric motility index in a dose-dependent manner (P Ͻ 0.05, vs. saline). Pretreatment with atropine completely abolished the motilin-induced gastric phase III contractions. On the other hand, in the free-feeding condition, the suncus showed a relatively long fasting period in the light phase followed by spontaneous gastric phase III contractions. The results suggest that the suncus has almost the same gastrointestinal motility and motilin response as those found in humans and dogs, and we propose the suncus as a new small model animal for studying gastrointestinal motility and motilin in vivo.suncus; migrating motor complex; motilin; ghrelin; gastric motility DURING A FASTED STATE, THE stomach and small intestine undergo a temporally coordinated cyclic motor pattern known as migrating motor complex (MMC) in dogs (38) and humans (44). It has been established that these coordinated contractions consist of three phases, phase I (period of motor quiescence), phase II (period of preceding irregular contractions), and phase III (period of clustered potent contractions), and the MMC is stimulated by endogenous motilin that is released in the fasted state.Motilin was originally purified from porcine intestinal mucosa in the 1970s, and its molecular structure was determined to be a 22-amino-acid polypeptide. It has been demonstrated that plasma motilin is released at ϳ100-min intervals at the interdigestive state (20,21). Physiological study of motilin in vivo has been mainly performed by using dogs and humans, and endogenous motilin and exogenous motilin have been shown to induce phase III contractions through the cholinergic pathway because atropine pretreatment completely abolished the motilin-induced contra...
Motilin and ghrelin are the gastrointestinal (GI) hormones released in a fasting state to stimulate the GI motility of the migrating motor complex (MMC). We focused on coordination of the ghrelin/motilin family in gastric contraction in vivo and in vitro using the house musk shrew (Suncus murinus), a ghrelin- and motilin-producing mammal. To measure the contractile activity of the stomach in vivo, we recorded GI contractions either in the free-moving conscious or anesthetized S. murinus and examined the effects of administration of motilin and/or ghrelin on spontaneous MMC in the fasting state. In the in vitro study, we also studied the coordinative effect of these hormones on the isolated stomach using an organ bath. In the fasting state, phase I, II, and III contractions were clearly recorded in the gastric body (as observed in humans and dogs). Intravenous infusion of ghrelin stimulated gastric contraction in the latter half of phase I and in the phase II in a dose-dependent manner. Continuous intravenous infusion of ghrelin antagonist (d-Lys3-GHRP6) significantly suppressed spontaneous phase II contractions and prolonged the time of occurrence of the peak of phase III contractions. However, intravenous infusion of motilin antagonist (MA-2029) did not inhibit phase II contractions but delayed the occurrence of phase III contractions of the MMC. In the in vitro study, even though a high dose of ghrelin did not stimulate contraction of stomach preparations, ghrelin administration (10(-10)-10(-7) M) with pretreatment of a low dose of motilin (10(-10) M) induced gastric contraction in a dose-dependent manner. Pretreatment with 10(-8) M ghrelin enhanced motilin-stimulated gastric contractions by 10 times. The interrelation of these peptides was also demonstrated in the anesthetized S. murinus. The results suggest that ghrelin is important for the phase II contraction and that coordination of motilin and ghrelin are necessary to initiate phase III contraction of the MMC.
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