title: Coordination of motilin and ghrelin regulates the migrating motor complex of gastrointestinal motility in Suncus murinus.
abstract: 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.
authors.affiliation: Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan.
authors.forename: Anupom
authors.initials: A
authors.lastname: Mondal
authors.forename: Zuoyun
authors.initials: Z
authors.lastname: Xie
authors.forename: Yuki
authors.initials: Y
authors.lastname: Miyano
authors.forename: Chihiro
authors.initials: C
authors.lastname: Tsutsui
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sakata
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kawamoto
authors.forename: Sayaka
authors.initials: S
authors.lastname: Aizawa
authors.forename: Toru
authors.initials: T
authors.lastname: Tanaka
authors.forename: Sen-ichi
authors.initials: S
authors.lastname: Oda
authors.forename: Takafumi
authors.initials: T
authors.lastname: Sakai
mesh_terms: D000818:Animals; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D054439:Ghrelin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D009037:Motilin / Q000494:pharmacology*; D016065:Myoelectric Complex, Migrating / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D012788:Shrews / Q000502:physiology*
chemical_list: C520836:GHRP-6, Lys(3)-; D054439:Ghrelin; C528741:MA-2029; D009842:Oligopeptides; D009037:Motilin