The role of the ATP--adenylate cyclase--cAMP system and its pharmacological regulation in the development of gastric hypersecretion and ulceration.

Abstract

The role and pharmacological regulation of the ATP-adenylate-cyclase--cAMP system were studied in the mucosa of the gastric fundus, and in the forestomach, of pylorus-ligated rats to elucidate the development of gastric hypersecretion and ulceration. (1) cAMP content of the tissue of the fundus mucosa and of the forestomach decreased before the significant increase of gastric H+ output and ulcer development; (2) the gastric H+ outputs depended on the breakdown of ATP in the fundus mucosa; (3) the gastric H+ secretion was inhibited in a dose-dependent way by theophylline, epinephrine and cimetidine; (4) the inhibition of gastric H+ secretion by epinephrine , theophylline or epinephrine plus theophylline associated with a significant increase in the mucosal cAMP of the gastric fundus (5) the significant increase in gastric H+ secretion due to histamine associated with a significant decrease in fundic mucosal cAMP; (6) the gastric H+ secretion could be inhibited dose-dependently by ADP, AMP, cyclic 2', 3'-AMP and cAMP; (7) the inhibition of gastric H+ secretion by cimetidine developed without and with histamine application in pylorus-ligated rats; (8) the histamine on gastric H+ secretion could not be stimulated further with theophylline (9) no significant correlation was found between the mucosal cAMP level and the gastric H+ secretion and/or between the decrease of mucosal cAMP content and gastric H+ secretion. It has been concluded that in pylorus-ligated rats (1) the gastric H+ secretion is an ATP-dependent process; (2) the cAMP system has an inhibitory effect as regards the development of gastric hypersecretion and of ulceration; (3) histamine and cimetidine show no close correlation with the cAMP system; (4) an extracellular and intracellular feed-back mechanism system exists between th ATP-membrane-bound ATPase-ADP and the ATP--adenylate cyclase--cAMP systems in the background of the development of gastric hypersecretion and ulceration.