Cisapride inhibits meal-stimulated gastric acid secretion and post-prandial gastric acidity in subjects with gastro-oesophageal reflux disease.
OBJECTIVE
KCNQ1 potassium channels in human gastric parietal cells are thought to be involved in gastric acid secretion. As cisapride can inhibit similar channels in other tissues and is an effective treatment for nocturnal heartburn, we examined the effects of cisapride on gastric and oesophageal acidity, gastric emptying and heartburn severity in subjects with gastro-oesophageal reflux disease.


METHODS
Subjects (n = 11) had suffered from heartburn four times or more per week for at least 6 months. Gastric pH and oesophageal pH were measured before, during and after a standard meal ingested over 15 min. Each subject received placebo or 10 mg cisapride orally, 30 min before the beginning of the meal. Meal-stimulated gastric acid secretion was calculated from the amount of HCl required to titrate the homogenized standard meal to pH 2 in vitro and the time required for the pH of the ingested meal to decrease to pH 2 in vivo. Heartburn severity was assessed at 15-min intervals beginning at the end of the meal. Gastric emptying of solids was measured using a [(13)C]-octanoic acid breath test.


RESULTS
Cisapride significantly decreased meal-stimulated gastric acid secretion by 20%, decreased integrated gastric and oesophageal acidity by 50-60% and transiently increased the expiration of (13)CO(2). Cisapride did not significantly alter heartburn severity.


CONCLUSIONS
The cisapride-induced decreases in meal-stimulated gastric acid secretion, gastric acidity and oesophageal acidity in subjects with gastro-oesophageal reflux disease can account for its beneficial clinical effects. These results also raise the possibility that gastric KCNQ1 potassium channels are important in meal-stimulated gastric acid secretion and possibly in the pathophysiology of gastro-oesophageal reflux disease.
Gardner
J D
JD
Science for Organizations, Inc., Chatham, NJ 07928, USA. gardnerj@bellatlantic.net
Rodriguez-Stanley
S
S
Robinson
M
M
Miner
P B
PB
D000328:Adult; D020117:Cisapride / Q000494:pharmacology* / Q000627:therapeutic use; D018592:Cross-Over Studies; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D005746:Gastric Emptying / Q000187:drug effects; D005764:Gastroesophageal Reflux / Q000188:drug therapy / Q000503:physiopathology*; D005765:Gastrointestinal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006356:Heartburn / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D017366:Serotonin Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use
D005765:Gastrointestinal Agents; D017366:Serotonin Receptor Agonists; D020117:Cisapride