LOXIGLUMIDE INHIBITS CHOLECYSTOKININ STIMULATED SOMATOSTATIN SECRETION AND SIMULTANEOUSLY ENHANCES GASTRIC-ACID SECRETION IN HUMANS

In vitro studies have demonstrated that cholecystokinin releases somat ostatin from the gastric mucosa. To date, there is no information abou t the in vivo significance of this finding in man. Therefore, we have studied the effect of infusion of cholecystokinin resulting in plasma concentrations within the range found after meal-stimulation, on somat ostatin release and on gastric acid secretion. In addition we have stu died these functions during infusion of the type A cholecystokinin rec eptor antagonist loxiglumide. In eight healthy subjects, basal gastric acid secretion was distinctly stimulated by cholecystokinin. The effe ct of cholecystokinin on gastric acid secretion was markedly enhanced by loxiglumide. Cholecystokinin also significantly stimulated somatost atin output into the gastric lumen, but not into the systemic circulat ion. Somatostatin output into the gastric lumen during infusion of cho lecystokinin was abolished by loxiglumide. The data indicate that on t he one hand circulating cholecystokinin, like gastrin, stimulates gast ric acid secretion probably by binding to less specific type B recepto rs on parietal cells that are not blocked by loxiglumide, but on the o ther hand that cholecystokinin, in contrast to gastrin, also inhibits gastric acid secretion probably by binding to specific type A receptor s present on somatostatin producing D-cells in the gastric mucosa, tha t are blocked by loxiglumide.