EFFECT OF CHOLECYSTOKININ-A-RECEPTOR BLOCKADE ON ESOPHAGEAL MOTILITY

Objective: The cholecystokinin (CCK)-A-receptor antagonist loxiglumide , was used to evaluate the effects of exogenously infused and endogeno usly released CCK on oesophageal motility in 22 healthy male volunteer s. Design and methods: In the first set of experiments, step-wise dose s of CCK-8 (3.3, 10 and 30 ng/kg/h) were infused with and without a ba ckground of loxiglumide (10 mg/kg/h). In the second and third sets of experiments, saline and loxiglumide were infused in the interdigestive state with concomitant duodenal perfusion of a mixed liquid meal. Oes ophageal motility was recorded during each experiment with a sleeve se nsor straddling the lower oesophageal sphincter.Results: Lower oesopha geal sphincter pressure decreased from 20.5 +/- 2.4 to 13.4 +/- 2.5 mm Hg (P < 0.01) and amplitude, area and contractility of distal oesophag eal peristaltic contractions were slightly reduced following 30 ng/kg/ h CCK-8 (P < 0.05). A background of loxiglumide eradicated these effec ts. Loxiglumide did not change interdigestive lower oesophageal sphinc ter pressure. Duodenal meal perfusion decreased lower oesophageal sphi ncter pressure from 25.8 +/- 2.9 to 17.0 +/- 2.4 mmHg (P < 0.01). Loxi glumide eliminated this postprandial decrease of lower oesophageal sph incter pressure [24.3 +/- 2.8 (basal) compared with 23.2 +/- 2.6 mmHg (loxiglumide); P < 0.001 compared with duodenal perfusion without loxi glumide]. Loxiglumide did not have a significant effect on oesophageal peristaltic contractions. Conclusions: (1) Loxiglumide is a specific CCK-receptor antagonist at the oesophageal level. (2) CCK is not a maj or regulator of interdigestive oesophageal motility, and (3) CCK is a major regulator of postprandial lower oesophageal sphincter tone. This raises the question of whether CCK-A-receptor antagonists could be va luable in gastro-oesophageal reflux disease.