Regulation of catecholamine synthesis in rat brain synaptosomes.

Abstract

Abstract— Catecholamine synthesis in synaptosomal preparations of rat striatum, cortex and brain stem was investigated. The striatum had much higher activity than either the cortex or brain stem. Equilibration of labelled tyrosine between tissue and incubation medium was completed within 2 min. The apparent Km of tyrosine hydroxylase (EC 1.14.3a) and of the overall catecholamine synthetic pathway were both approximately 5 ± 10−6m for tyrosine. The following amines were found to inhibit striatal dopamine synthesis: dopamine, 25% inhibition at 5 ± 10−7m; noradrenaline, 25% inhibition at 5 ± 10−6m;and serotonin, 30% inhibition at 10−5m. The catecholamine‐induced inhibition of synthesis was antagonized by pre‐incubation with cocaine. Increasing the potassium concentration from 5 to 55 mm caused a release of amines into the medium which was accompanied by a 40% increase in dopamine synthesis, when synthesis was measured during the first 5 min of exposure to elevated potassium. These results indicate that synaptosomal catecholamine synthesis is inhibited by increases in intra‐synaptosomal amine levels, and that short‐term exposure to depolarizing concentrations of potassium can increase synthesis.