Kainate receptors coupled to the evoked release of [3H]-gamma-aminobutyric acid from striatal neurons in primary culture: potentiation by lithium ions.

The pharmacological properties and modulation by lithium of the kainate (KA) receptor system coupled to the evoked release of [3H]-gamma-aminobutyric acid [( 3H]GABA) from purified populations of striatal neurons in primary culture were examined. KA evoked a dose-dependent (EC50, 100 microM) and saturable increase in [3H]GABA release from striatal neurons that was unaffected by the removal of extracellular calcium and resistant to the actions of tetrodotoxin. The release of [3H]GABA evoked by 100 microM KA was attenuated in a dose-dependent manner by the following excitatory amino acid antagonists (IC50):6-cyano-2, 3-dihydroxy-7-nitroquinoxaline (2 microM),2,3-dihydroxy-6,7-dinitroquinoxaline (2 microM), kynurenate (0.3 mM), and gamma-D-glutamylglycine (2 mM). The antagonist properties of 6-cyano-2,3-dihydroxy-7-nitroquinoxaline, kynurenate, and gamma-D-glutamylglycine were competitive in nature, inducing parallel rightward shifts of the KA dose-response curves. At concentrations at which it did not significantly increase basal levels of [3H]GABA release, quisqualate attenuated in a dose-dependent manner (IC50, 10 microM) the release due to 100 microM KA. The quisqualate receptor agonist alpha-amino-3-hydroxyisoxazolepropionic acid (AMPA), however, exerted a biphasic effect on 100 microM KA-evoked release of [3H]GABA. At lower concentrations of AMPA (0.1-10 microM), the release due to 100 microM KA was potentiated 25-50%; at higher concentrations (greater than 10 microM) AMPA induced a dose-dependent (IC50, 100 microM) attenuation of KA-evoked release. The release of [3H]GABA due to 100 microM KA was significantly potentiated by the replacement of sodium with lithium in the extracellular medium. A significant potentiation (20-30%) was detected with as little as 5-10 mM lithium, and maximal effects (100-110% increase) were obtained with 50-75 mM lithium. Replacement of sodium with choline or N-methyl-D-glucamine could not mimic the actions of lithium. Lithium (25 mM) also induced a 4-fold increase in the levels of endogenous GABA release due to 100 microM KA. Whole-cell voltage-clamp recordings of these striatal neurons indicated that the 100 microM KA-induced inward current was not significantly altered in the presence of 25 mM lithium. Lithium attenuated vasoactive intestinal polypeptide-stimulated cyclic AMP formation by 50%, with a dose dependence similar to that of its actions on KA-evoked release. The results of this study demonstrate a distinct pharmacological profile for the KA receptor system coupled to the evoked release of [3H]GABA from striatal neurons.(ABSTRACT TRUNCATED AT 400 WORDS)