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1 Human Nutrition Research
Center and Department of Gastroenterology and Hepatology,
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 · h1)
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.
esophageal manometry; barostat; fundic relaxation; cholecystokinin-A receptors; loxiglumide
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