Intracellular messenger role of cyclic GMP in exocrine pancreas

Abstract

THE response of cells to hormones and neurotransmitters is mediated by chemical regulators, of which calcium, adenosine cyclic 3′,5′-monophosphate (cyclic AMP) and guanosine cyclic 3′,5′-monophosphate (cyclic GMP) are considered to be of primary importance. The endogenous occurrence of cyclic GMP was discovered more than 10yr ago, but until recently its formation has been reported chiefly in association with the activation of cholinergic muscarinic receptors1,2. The description in the pancreas of a cyclic GMP-dependent protein kinase3, a cyclic GMP phospho-diesterase4, and the ability in vivo of cholecystokinin to increase cyclic GMP levels5, suggested a physiological role for cyclic GMP in the mediation of hormone action. We report here experiments on isolated guinea pig pancreatic slices, in which the hormone cholecystokinin (CCK) and the neurotransmitter acetylcholine (ACh) both produced a marked, transient increase in the tissue level of cyclic GMP, which preceded the release of secretory enzymes. Exposure of the isolated pancreatic slices to the hormone secretin evoked a more prolonged increase in cyclic AMP, without any significant effect on cyclic GMP.