Inhibition of vagally mediated gastric acid secretion by activation of central prostanoid EP3 receptors in urethane-anaesthetized rats.

1. We studied the effects of intracerebroventricular (i.c.v.) administration of prostanoid EP receptor ligands on vagally stimulated gastric acid secretion in rats anaesthetized with urethane. 2. Administration of misoprostol (EP3/EP2 receptor agonist) and sulprostone (EP3/EP1 receptor agonist) reduced vagally mediated gastric acid secretion in a dose-dependent manner (0.1, 0.3 and 1.0 nmol per animal). Butaprost (EP2 receptor agonist) (0.3 and 3.0 nmol per animal) was without effect. 17-Phenyl-omega- trinor PGE2 (EP1/EP3 receptor agonist) attenuated vagally mediated gastric acid secretion only at its highest dose (1.0 nmol per animal); this antisecretory effect was not prevented by pretreatment with SC-19220 (selective EP1 receptor antagonist) (20 nmol per animal, i.c.v.). 3. The potency of these test agents in attenuation of vagally mediated gastric acid secretion was as follows: misoprostol > or = sulprostone > > 17-phenyl-omega-trinor PGE2 > > > butaprost. These results suggest that activation of central prostanoid EP3 receptors induces inhibition of vagally mediated gastric acid secretion in rats.