Role of cyclic GMP in gastrin secretion from rat antral mucosae in organ culture.

Abstract

Rat antral mucosae maintained for 6 h in organ culture responded to carbamylcholine with a significant increase in endogenous cyclic GMP production and gastrin secretion. The acetylcholine analogue exerted a stimulatory action within a defined concentration range: exposure of antral explants to carbachol concentrations greater than the optimal stimulatory dose was accompanied by a marked decrease in both cyclic GMP production and gastrin release. Exogenous 8-Br-cyclic GMP (1 mM) significantly augmented gastrin secretion into the culture media during 6-12 h culture periods. Cycloheximide (0.1 mM) and the Ca2+ channel-blocker verapamil (5 microM) prevented 8-Br-cyclic GMP from acting as a gastrin secretagogue. Addition of cyclic somatostatin-14 (0.1 mM) to culture media was attended by complete inhibition of 8-Br-cyclic GMP-stimulable gastrin secretion. These results provide evidence that cyclic GMP may play a mediatory role in the coupling of gastrin secretory processes to agonist stimulation. It would seem that the secretagogue action of 8-Br-cyclic GMP requires unabated Ca2+ transmembrane fluxes and protein biosynthesis. Since somatostatin-14 abrogates the stimulatory effect of 8-Br-cyclic GMP on antral gastrin secretion, it is surmised that the inhibitory tetradecapeptide acts at a locus (or loci) distal to domains involved in the actual generation of the cyclic nucleotide.