Biochemical basis of action of gastrointestinal hormones

Abstract

The actions of secretin and VIP on pancreatic enzyme secretion result from their abilities to activate adenylate cyclase and increase cellular cyclic AMP. The actions of cholecystokinin, cholinergic agents, caerulein, bombesin, litorin, physalaemin, and eledoisin on pancreatic enzyme secretion result from their abilities to cause release of bound cellular calcium. Although this action causes an increase in cellular cyclic GMP, it remains to be determined whether or not cyclic GMP is a mediator of the action of secretagogues on pancreatic enzyme secretion. Secretagogues that increase cyclic AMP do not alter calcium transport or cyclic GMP and do not modify the changes in calcium transport or cyclic GMP caused by other agents. Secretagogues that cause release of cellular calcium and increase cyclic GMP do not alter cyclic AMP and do not cause major changes in the increase in cyclic AMP produced by other secretagogues. Although the two mechanisms of action of pancreatic secretagogues are initially distinct, they interact at some presently undefined step, and this interaction results in potentiation of enzyme secretion. The finding that two agents potentiate each other has important implications for the mechanisms of action of the two agents and has potential therapeutic applications.