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.
Masclee
A A
AA
Department of Gastroenterology-Hepatology, University Hospital Leiden, The Netherlands.
Jansen
J B
JB
Rovati
L C
LC
Lamers
C B
CB
D000328:Adult; D000368:Aged; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000502:physiology; D002792:Cholestyramine Resin / Q000494:pharmacology*; D004943:Esophagogastric Junction / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011312:Pressure; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*
D011949:Receptors, Cholecystokinin; D002792:Cholestyramine Resin; C053737:loxiglumide; D002766:Cholecystokinin; D011377:Proglumide