CHARACTERIZATION OF THE ANTISECRETORY ACTION OF PROSTAGLANDIN-D(2) IN THE RAT COLON

Previous studies have shown that prostaglandin D2 (PGD2) inhibits neuronally mediated secretion in the rat colon. This antisecretory action of PGD2 was further characterized by the use of a prostaglandin D receptor blocker. Prostaglandin D2 inhibited the neuronally mediated short-circuit current evoked by prostaglandin I2, which represents Cl- secretion. The concentration-response curve for the inhibition by PGD2 was shifted to the right in the presence of the prostaglandin D receptor blocker, AH 6809. AH 6809 had no effect on the short-circuit current response induced by prostaglandin E2 or iloprost, a stable prostaglandin I2 analogue, suggesting an interaction of the blocker with receptors specific for PGD2. A direct interaction of PGD2 with enteric neurones was studied by determining its effect on acetylcholine release from enteric neurones preloaded with [H-3]choline. Prostaglandin D2 suppressed H-3 release induced by electric field stimulation. It had, however, no effect on the release induced by depolarization with potassium. The results suggest that the inhibitory action of PGD2 on enteric cholinergic neurones is mediated by prostaglandin D receptors.