Modulatory action of prostaglandin D2 on the release of 3H-norepinephrine from rat cerebellar slices.

Abstract

The modulatory action of prostaglandin D2 (PGD2) on the high-K+-induced release of 3H-norepinephrine (3H-NE) from rat cerebellar slices was investigated in relation to the presynaptic feedback mechanisms for the NE release. PGD2 (10(-7)-10(5) M) dose-dependently suppressed the release of 3H-NE. The 3H-NE release was also dose-dependently decreased by 10(-10)-5 X 10(-9) M clonidine and increased by 10(-9)-10(-6) M yohimbine, and there was an antagonism between clonidine and yohimbine, indicating the presence of an alpha 2-adrenoceptor-mediated negative feedback mechanism in the rat cerebellum. The inhibitory action of clonidine was not additive to that of PGD2, while there appeared to be an additiveness between the effects of PGD2 and yohimbine. The 3H-NE release was increased by I-isoproterenol and decreased by I-propranolol, but only at concentrations higher than 10(-6) M. PGD2 nearly abolished the actions of these beta-adrenergic agents, and the 3H-NE release remained at a level similar to that induced by 10(-5) M PGD2 alone. Based on these results, it was tentatively suggested that PGD2 inhibits the 3H-NE release by a mechanism independent of adrenoceptor-mediated feedback mechanisms.