Endogenous cholecystokinin in postprandial lower esophageal sphincter function and fundic tone in humans

Transient lower esophageal sphincter (LES) relaxations (TLESRs) are the mai n underlying mechanism of gastroesophageal reflux. Although CCK acts throug h CCK-A receptors to increase the TLESRs induced by gastric distension, the respective roles of endogenous CCK and fundic tone in triggering postprand ial TLESRs remain unknown. The aim of this study was to determine the effec t of the CCK-A receptor antagonist, loxiglumide, on postprandial LES functi on and fundic tone in humans. LES motor events and fundic tone were simulta neously monitored in two groups of healthy volunteers. Recordings were perf ormed during fasting and for 3 h after a liquid meal (200 ml/200 kcal) admi nistered either orally or intraduodenally at a rate mimicking gastric empty ing. Each subject received loxiglumide (10 mg.kg(-1).h(-1)) or saline (cont rol) in randomized order, which was started 40 min before the meal and main tained for 3 h thereafter. After the oral meal, loxiglumide significantly r educed TLESRs (P = 0.002) without significantly affecting LES pressure and fundic tone. After duodenal infusion of the meal, loxiglumide totally aboli shed the increase in TLESRs, reduced LES pressure fall (P < 0.02), and stro ngly inhibited fundic relaxation (P = 0.0001). We concluded that endogenous CCK is involved in the postprandial control of both LES function and fundi c tone through activation of CCK-A receptors.