Elevation of plasma noradrenaline levels in urethane-anaesthetized rats by activation of central prostanoid EP3 receptors

Abstract

1. We studied the effects of intracerebroventricular (i.c.v.) administration of prostaglandin E2 (PGE2) and its receptor subtype ligands on plasma levels of catecholamines in urethane-anaesthetized rats. 2. Administration of PGE2 (0.15, 0.3 and 1.5 nmol per animal, i.c.v.) dose-dependently elevated plasma levels of noradrenaline (NA), while the levels of adrenaline were not affected. 3. Administration of sulprostone (EP3/EP1 agonist) and misoprostol (EP3/EP2 agonist) effectively elevated plasma NA levels in a dose-dependent manner (0.1, 0.3, and 1.0 nmol per animal). Butaprost (EP2 agonist) (0.3, 1.0 and 3.0 nmol per animal) was without effect. 17-Phenyl-omega-trinor PGE2 (EP1/EP3 agonist) effectively elevated plasma NA levels only at its highest dose (1.0 nmol per animal), but this elevation was not attenuated by pretreatment with SC-19220 (selective EP1 antagonist) (20 nmol per animal, i.c.v.). 4. The potency of these test agents in elevating plasma levels of NA was as follows; misoprostol > sulprostone > PGE2 > > 17-phenyl-omega-trinor PGE2 > > > butaprost. These results suggest that activation of central prostanoid EP3-receptors induces central sympathetic outflow in rats.