CHOLECYSTOKININ IS A PHYSIOLOGICAL REGULATOR OF GASTRIC-ACID SECRETION IN MAN

CCK8 is a poor stimulant of gastric acid secretion in vivo, but is equ ipotent to gastrin-17 (G17) in in vitro systems. To further evaluate t he role of cholecystokinin (CCK) in regulating acid output in humans, dose-response curves were constructed to CCK8 or G17 (6.4-800 pmol kg( -1) per h) with and without a specific CCK-A receptor antagonist (loxi glumide). During loxiglumide infusion, G17-stimulated acid output was unchanged, whereas CCK8-stimulated secretion increased significantly. Gastric somatostatin-14 release increased fivefold with CCK8 alone, bu t was blocked with loxiglumide administration. These data suggest that CCK8 directly stimulates acid secretion by binding to a CCK-B/gastrin receptor on parietal cells, but at the same time inhibits acid respon ses by stimulating gastric somatostatin release to a CCK-A receptor-me diated pathway. To test which action of CCK is relevant under physiolo gical circumstances, the effect of loxiglumide on fasting and post-pra ndial acidity was measured through continuous pH-metry. After eating, gastrin levels increased fourfold compared to controls with concomitan t increases in acid secretion. These results suggest that post cibum, CCK is an inhibitor of acid secretion by regulating gastrin through lo cal somatostatin; they support the hypothesis that CCK acts as an ente rogastrone.