title: Endogenous cholecystokinin in postprandial lower esophageal sphincter function and fundic tone in humans.
abstract: Transient lower esophageal sphincter (LES) relaxations (TLESRs) are the main underlying mechanism of gastroesophageal reflux. Although CCK acts through CCK-A receptors to increase the TLESRs induced by gastric distension, the respective roles of endogenous CCK and fundic tone in triggering postprandial TLESRs remain unknown. The aim of this study was to determine the effect of the CCK-A receptor antagonist, loxiglumide, on postprandial LES function and fundic tone in humans. LES motor events and fundic tone were simultaneously monitored in two groups of healthy volunteers. Recordings were performed during fasting and for 3 h after a liquid meal (200 ml/200 kcal) administered either orally or intraduodenally at a rate mimicking gastric emptying. Each subject received loxiglumide (10 mg. kg-1. h-1) or saline (control) in randomized order, which was started 40 min before the meal and maintained for 3 h thereafter. After the oral meal, loxiglumide significantly reduced TLESRs (P = 0.002) without significantly affecting LES pressure and fundic tone. After duodenal infusion of the meal, loxiglumide totally abolished the increase in TLESRs, reduced LES pressure fall (P < 0.02), and strongly inhibited fundic relaxation (P = 0.0001). We concluded that endogenous CCK is involved in the postprandial control of both LES function and fundic tone through activation of CCK-A receptors.
authors.affiliation: Human Nutrition Research Center and Department of Gastroenterology and Hepatology, University of Nantes, 44035 Nantes, France.
authors.forename: F
authors.initials: F
authors.lastname: Zerbib
authors.forename: S
authors.initials: S
authors.lastname: Bruley Des Varannes
authors.forename: C
authors.initials: C
authors.lastname: Scarpignato
authors.forename: V
authors.initials: V
authors.lastname: Leray
authors.forename: M
authors.initials: M
authors.lastname: D'Amato
authors.forename: C
authors.initials: C
authors.lastname: Rozé
authors.forename: J P
authors.initials: JP
authors.lastname: Galmiche
mesh_terms: D000328:Adult; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology*; D004386:Duodenum; D004435:Eating / Q000502:physiology*; D004750:Enteral Nutrition; D004943:Esophagogastric Junction / Q000187:drug effects / Q000502:physiology*; D005215:Fasting; D005260:Female; D005748:Gastric Fundus / Q000187:drug effects / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D008297:Male; D008365:Manometry; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology*; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors
chemical_list: D006727:Hormone Antagonists; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; C053737:loxiglumide; D002766:Cholecystokinin; D011377:Proglumide