Presynaptic effects of gamma-aminobutyric acid on norepinephrine release and uptake in rat pineal gland.

The effect of tau-aminobutyric acid (GABA) on pineal norepinephrine (NE) release was examined in vitro in the rat pineal gland. Exposure of pineal explants previously loaded with 3H-NE to 1-100 microM GABA caused a dose-dependent decrease of 3H-NE release triggered by 60 mM K+, with a threshold GABA concentration of 1 microM and IC50 of about 10 microM. The inhibitory effect of GABA was mimicked by the type B GABA agonist baclofen, displaying a similar dose-response relationship as GABA. The type A GABA agonist muscimol increased depolarization-induced 3H-NE release, while the co-incubation with GABA and the type A receptor antagonist bicuculline augmented significantly GABA's depressive effect on 3H-NE release. Bicuculline alone brought about a significant decrease of 3H-NE release. Neither GABA, nor baclofen, muscimol or bicuculline, modified the spontaneous pineal 3H-NE efflux. Assessment of 3H-NE uptake at a low NE concentration (0.5 microM) indicated that GABA decreased it in a dose-dependent manner (IC50 = 100 microM) through an effect blocked by bicuculline and mimicked by muscimol but not by baclofen; at a 5 microM-3H-NE concentration a bicuculline-sensitive GABA augmentation of uptake was found. A kinetic analysis study of the pineal NE uptake process indicated that GABA augmented both Vmax and Km of transmitter uptake. These results indicate that GABA may be a significant regulatory signal for rat pineal sympathetic synapses.