Prostaglandins Stimulate and Inhibit Acid Secretion in Amphibian Fundic Mucosa1

Stripped gastric fundic mucosae of Rana catesbeianawere mounted between two halves of a lucite chamber, and acid secretion was measured during continuous monitoring of transmucosal potential difference (PD), resistance (R), and short-circuit current (Isc). At low concentrations (<10-6M), 16,16-dimethyl prostaglandin E2(16,16dmPGE2) is inhibitory to the H+secretory mechanism, while at higher concentrations (>10-6M), 16,16dmPGE2stimulates H+secretion without significant change in electrical measurements. The stimulatory effect which is observed with titration at a luminal pH of either 4.8 or 7.4 shows tachyphylaxis, is abolished by metiamide (1 × 10-3M) but not by atropine (1 × 10-6M), and is prevented or reduced by pretreatment with compound 48/80 (1 × 10-4g/ml), a substance which releases histamine from mast cells or by heparin which prevents release of histamine from mast cells. Similar stimulatory effects were observed with PGE1, PGF2α, and PGI2at 1 × 10-5M, with the magnitude of the effect being PGE1≥ 16,16dmPGE2> PGF2α> PGI2.On the other hand, in tissues pretreated with compound 48/80, 16,16dmPGE2(10-9to 10-5M) caused inhibition of histamine-stimulated H+secretion only. These findings suggest that in addition to their inhibitory effects, prostaglandins (PGs) at higher concentrations stimulate H+secretion by releasing endogenous histamine from mast cells.