Effect of cholestyramine and cholecystokinin receptor antagonist CR1505 (loxiglumide) on lower esophageal sphincter pressure in man.

Cholecystokinin (CCK) decreases lower esophageal sphincter pressure (LESP) in man. Cholestyramine, a nonabsorbable bile salt binding resin, stimulates endogenous CCK secretion. We have investigated the effect of oral ingestion of 16 g cholestyramine without and with infusion of the CCK receptor antagonist CR1505 (loxiglumide, 15 mg/kg/90 min) on LESP in seven healthy subjects. LESP was recorded for 90 min, in 10-min intervals, with the pull-through technique using a four-lumen water-perfused catheter. Oral ingestion of cholestyramine resulted in a significant (P < 0.05) decrease in LESP, starting from 10 min and continuing during the entire experiment (basal LESP: 11.8 +/- 2 mm Hg, minimal value reached during cholestyramine: 7.3 +/- 1 mm Hg; P < 0.05). Pretreatment with loxiglumide completely antagonized the effect of cholestyramine on LESP. Infusion of loxiglumide without cholestyramine did not affect basal LESP. It is concluded that: (1) cholestyramine significantly reduces LESP; (2) this reduction in LESP does not occur after pretreatment with loxiglumide, indicating that cholestyramine influences LESP through CCK release; and (3) basal LESP is not regulated by CCK.