Abstract

Dopamine in the rat corpus striatum declines biphasically after intraperitoneal injection of 0.81 nmole/kg of α-methyl-p-tryosine methyl ester. This confirms the results of Javoy and Glowinski [(1971) J. Neurochem., 18: 1305-1311]. The rapid initial decline in striatal dopamine is coincident with p-hydroxyamphetamine and p-hydroxynorephedrine concentrations of 1.2 and 8.2 nmoles/g of brain, respectively. Similar concentrations are present in the striatum. p-Hydroxyamphetamine and p-hydroxynorephedrine may be responsible for the fast initial decline in striatal dopamine after treatment with α-methyl-p-tyrosine methyl ester, because these compounds change the kinetics of striatal dopamine, presumably by increasing its efflux. Moreover, the conversion index of striatal labeled tyrosine to striatal dopamine is inhibited only 53% between 5 and 15 min after injection of α-methyl-p-tyrosine methyl ester. We propose a new method for calculating the turnover rate of striatal dopamine, based on normalized plots of the change with time of the specific activity of striatal tyrosine and dopamine after injection of tracer amounts of [³H]tyrosine. The transformation constant (τ) is defined by the fractional rate constant of tyrosine (k_Tyr) and is calculated as equal to 1/k_Tyr. This kinetic analysis yields an estimate of the striatal dopamine turnover rate in agreement with values estimated by other methods. The experimental data are incompatible with a two-compartment model of dopamine: a functional compartment (26% of the store) and a main storage compartment (74% of the store) with k values of 4.6 and 0.34 hr^-1, respectively, as proposed by Javoy and Glowinski. Calculations show that the 0.34 hr^-1 rate for a single striatal dopamine compartment exceeds the limits imposed by the change with time of striatal dopamine specific radioactivity after a tracer injection of [³H]tyrosine.