DOPAMINE SYNTHESIS IN RAT-BRAIN STRIATAL SYNAPTOSOMES .1. CORRELATIONS BETWEEN VERATRIDINE-INDUCED SYNTHESIS STIMULATION AND ENDOGENOUS DOPAMINE RELEASE

Abstract

The effects of depolarizing concentrations of veratridine were studied to determine the degree to which dopamine synthesis stimulation was correlated with stimulated endogenous dopamine release in rat brain striatal synaptosomes. Incubations included cocaine and pargyline to prevent dopamine reuptake and metabolism, respectively. Veratridine produced a 44% increase in dopamine release in 10 min and a similar increase in synthesis rate. Preincubation with tetrodotoxin prevented the increase in both release and synthesis, while incubation in a Ca-free medium antagonized both responses approximately 50%. Addition of 1 mM ethylene glycol bis(.beta.-aminoethyl ether)-N,N''-tetraacetic acid to the Ca-free incubation medium further inhibited the release response but not the synthesis stimulation. In general the degree of synthesis stimulation produced by depolarizing agents such as veratridine can probably be correlated with their stimulation of dopamine release, suggesting either that transmitter release itself is a signal for synthesis stimulation, possibly by removal of feedback inhibition of tyrosine hydroxylase or that depolarizing agents increase synthesis through a secondary metabolic change that is either caused by, or at least accompanied by, transmitter release.