COPRESENCE OF PROSTAGLANDIN EP(2) AND EP(3) RECEPTORS ON GASTRIC ENTEROCHROMAFFIN-LIKE CELL CARCINOID IN AFRICAN RODENTS

Background and Aims: Prostaglandins (PGs) have important roles in the regulation of gastric acid secretion. The aim of this study was to exa mine the possible presence of PG receptors on the gastric enterochroma ffin-like (ECL) carcinoid of Mastomys natalensis, which might be a use ful model of normal ECL cells. Methods: A [H-3]PGE(2) binding experime nt was performed by using the ECL tumor membrane, and intracellular si gnal transduction was studied in the cells. In addition, Northern blot analysis using EP(2) and EP(3) receptor. complementary DNAs was condu cted. Results: [H-3]PGE(2) specifically bound to the tumor cell membra ne, and the binding was displaced by various PGs with a potency order of PGE(1) = PGE(2) > enprostil > PGF(2 alpha). Although PGE(1) and PGE (2) stimulated 5'-cyclic adenosine monophosphate (cAMP) production, ne ither PGF(2 alpha) nor enprostil had any effect. On the other hand, al l of PGE(1), PGE(2), PGF(2 alpha), and enprostil attenuated the forsko lin-induced cAMP production. Moreover, enprostil inhibited histamine r elease induced by forskolin. However, on pertussis toxin treatment, PG E(2) paradoxically enhanced the forskolin-induced increase of cAMP pro duction. Finally, the presence of EP(2) and EP(2) receptor messenger R NAs was confirmed by RNA blot analysis. Conclusions: The ECL carcinoid tumor cells of Mastomys seem to possess two subtypes of PGE receptor: EP(2) linked to cAMP production and EP(3) coupled with inhibitory gua nosine 5'-triphosphate-binding proteins mediating the inhibition of cA MP production.