title: Influence of motilin on gastric fundus tone and on meal-induced satiety in man: role of cholinergic pathways.
abstract: BACKGROUND
  Motilin agonists are strong gastroprokinetics, but their impact on symptoms in delayed gastric emptying has been disappointing. It has been speculated that it is due to the contractile effect of motilin agonists on the proximal stomach, but the pathway involved and the symptomatic consequences have been incompletely elucidated.
  
  
  OBJECTIVE
  To study whether motilin enhances proximal stomach tone and enhances meal-induced satiety and to evaluate whether this effect involves a cholinergic pathway.
  
  
  METHODS
  A gastric barostat was used to study, in healthy subjects, the effect of motilin (300 ng/kg/30 min i.v.) or saline on fasting gastric fundus tone and on post-prandial relaxation. To evaluate the involvement of a cholinergic pathway, atropine (12 microg/kg/h) was administered intravenously simultaneously with or before and during motilin infusion in the fasting state. Finally, a satiety drinking test was performed in 21 subjects twice after pretreatment with placebo or motilin and with placebo or atropine.
  
  
  RESULTS
  Administration of motilin caused a significant increase of fasting fundus tone expressed as decrease of the mean balloon volume (324 +/- 60 mL vs 213 +/- 62 mL, p < 0.05). Simultaneous administration of atropine and motilin did not generate a significant volume change (192 +/- 60 mL vs 181 +/- 83 mL, NS), but pretreatment with atropine alone induced a relaxation, and when motilin was added this revealed an ongoing contraction (192 +/- 24 mL vs 136 +/- 21 mL, p < or = 0.05). Motilin infusion also inhibited gastric accommodation (p < or = 0.05 vs placebo) and increased satiety during a satiety drinking test (p < or = 0.05 vs placebo).
  
  
  CONCLUSIONS
  Administration of motilin causes a contraction of the proximal stomach in humans and increases meal-induced satiety. The effect of motilin is atropine-resistant and involves a direct muscular pathway or a non-cholinergic neural pathway.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium.
authors.forename: Rosario
authors.initials: R
authors.lastname: Cuomo
authors.forename: Pieter
authors.initials: P
authors.lastname: Vandaele
authors.forename: Bernard
authors.initials: B
authors.lastname: Coulie
authors.forename: Theo
authors.initials: T
authors.lastname: Peeters
authors.forename: Inge
authors.initials: I
authors.lastname: Depoortere
authors.forename: Jozef
authors.initials: J
authors.lastname: Janssens
authors.forename: Jan
authors.initials: J
authors.lastname: Tack
mesh_terms: D000328:Adult; D001285:Atropine / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D004311:Double-Blind Method; D004435:Eating; D005215:Fasting; D005260:Female; D005748:Gastric Fundus / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009037:Motilin / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects*; D019518:Postprandial Period; D012527:Satiation / Q000187:drug effects* / Q000502:physiology
chemical_list: D018678:Cholinergic Agents; D009037:Motilin; D001285:Atropine