Prostaglandins Stimulate and Inhibit Acid Secretion in Amphibian Fundic Mucosa 1

Abstract

Abstract

Stripped gastric fundic mucosae of Rana catesbeiana were 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 (I _sc). At low concentrations (<10^-6 M), 16,16-dimethyl prostaglandin E₂ (16,16dmPGE₂) is inhibitory to the H⁺ secretory mechanism, while at higher concentrations (>10^-6 M), 16,16dmPGE₂ stimulates 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^-3 M) but not by atropine (1 × 10^-6 M), and is prevented or reduced by pretreatment with compound 48/80 (1 × 10^-4 g/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, PGF_2α, and PGI₂ at 1 × 10^-5 M, with the magnitude of the effect being PGE₁ ≥ 16,16dmPGE₂ > PGF_2α > PGI_2. On the other hand, in tissues pretreated with compound 48/80, 16,16dmPGE₂ (10^-9 to 10^-5 M) 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.