EFFECTS OF PROSTAGLANDINS ON GASTRIN-RELEASE FROM CANINE ANTRAL MUCOSAL CELLS IN PRIMARY CULTURE

Evidence in vivo indicates that endogenous and exogenous prostaglandin s can alter gastrin secretion. We have used primary cultures containin g canine antral G-cells to study the cellular actions of prostaglandin s on gastrin secretion, comparing the effects of prostaglandin E(2) (P GE(2)) and its synthetic analogue enprostil. Enprostil (10(-10)-10(-6) M) inhibited gastrin secretion in response to bombesin, carbachol, an d forskolin, the latter a receptor-independent activator of adenylate cyclase. This inhibition by enprostil was reversed by treatment with p ertussis toxin (200 ng/ml, 8 h). However, enprostil did not inhibit th e postreceptor stimuli 8-bromoadenosine 3',5'-cyclic monophosphate (10 (-3) M), calcium ionophore A-23187 (10(-7) M), or 4 beta-phorbol 12-my ristate 13-acetate (10(-8) M). In contrast, whereas PGE(2) inhibited f orskolin-stimulated gastrin release, PGE(2) did not inhibit the respon se to carbachol or bombesin in control cultures. However, in pertussis toxin-treated cultures, PGE(2) inhibition was reversed and, in contra st, the responses to bombesin, carbachol, and possibly forskolin were augmented. Indomethacin at a dose of 10(-5) M did not alter basal or b ombesin-stimulated gastrin secretion. However, the somatostatin antibo dy CURE-S6 enhanced the response to forskolin and enhanced inhibition by PGE(2), suggesting that endogenous somatostatin produced an inhibit ory tone in these cultures and excluding the possibility that PGE(2) a cted via release of endogenous somatostatin. Our data suggest that in cultured antral cells gastrin release is regulated by inhibitory and s timulatory prostaglandin mechanisms. The definitive localization of th ese mechanisms to G-cells or other antral cell types has to await the development of highly enriched G-cell preparations. Enprostil appears to selectively activate inhibitory mechanisms, whereas PGE(2) presumab ly interacts with both stimulatory and inhibitory mechanisms. Consider ation of these dual actions is essential to sorting out potential effe cts of endogenous prostaglandins on gastrin secretion.