Pharmacological characterization of pre- and postsynaptic prostanoid receptors in pig gastric fundus

Abstract

This study characterized the subtype of prostanoid receptors on the cholinergic neurones and smooth muscle cells in circularly oriented muscle strips of the pig gastric fundus. Tissues were electrically stimulated (40 V, 4 Hz, 0.25 ms, 2 min) to induce tritium outflow after incubation with [ 3H]-choline. Indomethacin increased the electrically induced tritium outflow, suggesting an inhibitory effect of endogenous prostanoids. In the presence of indomethacin, PGE 2>PGF 2 α >PGI 2 inhibited tritium release while the TP-receptor agonist U-46619 and PGD 2 had no effect. The EP 2-receptor agonist butaprost had no effect while the EP 1- and EP 3-receptor agonist sulprostone mimicked the effect of PGE 2. The effect of sulprostone was not affected by AH 6809, that antagonizes EP 1- and EP 2-receptors, suggesting the presence of presynaptic EP 3-receptors on the cholinergic nerve endings. All prostanoid receptor agonists, except butaprost, contracted the tissues concentration-dependently; the rank order of potency (U-46619>sulprostone>PGE 2>PGF 2 α >PGD 2=PGI 2) suggests the presence of TP- and EP 1- and EP 3-receptors on the circular smooth muscle cells.