Effect of H2-receptor antagonists, cimetidine and YM-11170, on serum gastrin levels in lumen-perfused rats.

To determine whether cimetidine increases serum gastrin levels by elevation of intragastric pH or by other mechanisms, the effects of two different H2-receptor antagonists, cimetidine and YM-11170, on serum gastrin levels were compared in rats with controlled intragastric pH. When the intragastric pH was maintained between 4.5 and 5.5, 2-10 mumol/kg of cimetidine increased serum gastrin levels significantly, whereas no significant increase was observed after 0.02-0.1 mumol/kg of YM-11170. This occurred despite the same extent of inhibition of histamine-stimulated acid secretion as with cimetidine. When the intragastric pH was fixed at 5.5, the serum gastrin responses to cimetidine were significantly greater than to saline or YM-11170. Therefore, the increase in serum gastrin levels by cimetidine is due neither to the elevation of intragastric pH nor the result of H2-receptor blockade, but is probably due to a direct action to release gastrin.