Prostaglandins inhibit secretion of histamine and pancreastatin from isolated rat stomach ECL cells

1 The present study examines the effect of naturally occurring prostanoids and prostaglandin (PG) congeners on gastrin- and pituitary adenylate cyclase-activating peptide (PACAP)-evoked histamine and pancreastatin secretion from isolated rat stomach ECL cells. 2 ECL cells (75-85% purity) were isolated from rat stomach using pronase digestion followed by repeated counter-flow elutriation and cultured for 48 h before secretion experiments. The release of histamine and pancreastatin was determined by radioimmunoassay. 3 None of the PGs tested stimulated the release of either histamine or pancreastatin. 4 PGE(1) and PGE(2) inhibited both gastrin- and PACAP-evoked histamine and pancreastatin secretion (IC(50)=1-2 x 10(-10) M). Most other naturally occuring prostanoids and PG congeners had no or little inhibitory effect. The PGE analogues misoprostol and sulprostone were more potent (IC(50)=0.9 x 10(-11) M and 2 x 10(-11) M respectively) than PGE(1) and PGE(2). The rank order of potency was misoprostol > sulprostone > PGE(1) = PGE(2), suggesting the involvement of the so-called EP(3) receptor. 5 The effects of PGs on the stomach ECL cells may be direct or indirect, for instance through the stimulated release of somatostatin from contaminating D cells (2-3%). However, the amount of somatostatin in the cell culture after 48 h was below the limit of detection, and somatostatin immunoneutralization did not prevent misoprostol from inhibiting secretion from the ECL cells. 6 The misoprostol-induced inhibition was reversed by pertussis toxin suggesting the involvement of G-protein subunits G alpha(0) and/or G alpha(i). 7 In view of the potency by which PGE(1), PGE(2), misoprostol and sulprostone inhibited the stimulated release of histamine and pancreastatin, we suggest that the ECL cells represent a primary target for prostaglandins acting via an EP3 receptor in the oxyntic mucosa. 8 The results suggest that the clinically useful effect of misoprostol as an anti-ulcer drug reflects its ability to inhibit stomach ECL-cell histamine secretion.