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 examine the possible presence of PG receptors on the gastric enterochromaffin-like (ECL) carcinoid of Mastomys natalensis, which might be a useful model of normal ECL cells. Methods: A [H-3]PGE(2) binding experiment was performed by using the ECL tumor membrane, and intracellular signal transduction was studied in the cells. In addition, Northern blot analysis using EP(2) and EP(3) receptor. complementary DNAs was conducted. Results: [H-3]PGE(2) specifically bound to the tumor cell membrane, 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, neither PGF(2 alpha) nor enprostil had any effect. On the other hand, all of PGE(1), PGE(2), PGF(2 alpha), and enprostil attenuated the forskolin-induced cAMP production. Moreover, enprostil inhibited histamine release induced by forskolin. However, on pertussis toxin treatment, PGE(2) paradoxically enhanced the forskolin-induced increase of cAMP production. Finally, the presence of EP(2) and EP(2) receptor messenger RNAs 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 guanosine 5'-triphosphate-binding proteins mediating the inhibition of cAMP production.