Stimulation of rat colonic mucosal prostaglandin synthesis by calcium and carbamylcholine: relationship to alterations in cyclic nucleotide metabolism.

The present study examined the relationships between prostaglandin (PG) synthesis and cyclic nucleotide metabolism in rat colonic mucosal slices. Ca2+, Ca2+ plus A23187 and carbamylcholine all increased [14C]-arachidonate release from prelabeled slices and stimulated production of PGE. Actions of A23187 and carbamylcholine required Ca2+ and were suppressed by tetracaine or mepacrine, whose known actions include inhibition of acyl hydrolase activity. Exogenous arachidonate or linoleate stimulated PGE synthesis in the absence of Ca2+ or in the presence of the inhibitors, suggesting a role for Ca2+ dependent acyl hydrolase activity in the mediation of the actions of Ca2+, A23187 and carbamylcholine on PGE synthesis. Accumulation of both cAMP and cGMP in colonic mucosal slices was enhanced by carbamylcholine, Ca2+, Ca2+ plus A23187, arachidonate or linoleate. Stimulatory actions of each of these agents on PGE production and cyclic nucleotide accumulation were inhibited by O2 exclusion or indomethacin (100 micrograms/ml). The results support a role for local PG production in the mediation of carbamylcholine and Ca2+ actions on cyclic nucleotides. Endogenous ionic, neurohumoral and dietary factors may modulate colonic mucosal PG synthesis and cyclic nucleotide content, and thereby influence the physiologic expression of the actions of these putative local cellular regulators.