Synthesis and release of serotonin by brain slices: Effect of ionic manipulations and cationic ionophores

Abstract

The effect of various ionic manipulations and cationic ionophores on the rates of release and synthesis of serotonin were investigated in brain slices prepared from adult male rats. Two depolarizing, univalent cationic ionophores, gramacidin (10 μg/ml) and valinomycin (10 μ/ml), and the non-depolarizing, calcium-specific ionophore, A23187 (190 μM), stimulated both the release and synthesis of serotonin in this tissue preparation. Electrical field depolarization of the brain slices also stimulated both the release and synthesis of serotonin, effects which were completely blocked by a calcium-free media and 1 mM EGTA or by 10 mM Mg 2+. Lithium partially blocked the release of serotonin by the stimulated brain slices, but markedly augmented the rates of serotonin biosynthesis. Although electrical stimulation significantly increased the rate of [ 3H]tryptophan uptake by the slices, the increased rates of release and synthesis of serotonin following treatment of the tissues with the ionophores and lithium were not associated with increased rates of tryptophan uptake. Furthermore, despite the inhibition of the release and synthesis of serotonin by stimulated slices incubated in the presence of magnesium or in the absence of calcium, rates of tryptophan uptake by the stimulated brain slice remained increased. These results taken together with the results of other studies suggest that release and synthesis of serotonin by the serotonergic neuron is tightly coupled to the ionic events attending depolarization and further argue than transcellular calcium fluxes may be of special importance in this regulation. These results do not support the postulate that regulation of serotonin release and synthesis is dependent upon substrate availability as a major variable.