Short-term and long-term regulation of tyrosine hydroxylase activity in retinal and mesolimbic dopamine-containing neuron

Abstract

Tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis (Levitt et al., 1965), has been shown to be regulated by changes in the specific activity of the enzyme molecules (enzyme activation) and by changes in the rate of TH biosynthesis (enzyme induction). Both activation and induction of TH have been observed in adrenal medulla and in central nervous system (CNS) norepinephrine-containing neurons (Mueller et al., 1969; Joh et al., 1973; Chuang and Costa, 1974; Reis et al., 1975; Roth et al., 1975; Lewander et al., 1977; Masserano and Weiner, 1979). In dopamine (DA)-containing neurons of brain, activation of TH has been observed following short-term increases in neuronal activity produced by either acute administration of antipsychotic drugs or direct electrical stimulation (Zivkovic et al., 1975; Murrin et al., 1976). This paper describes studies concerning the regulation of TH in DA-containing neurons in the CNS. The specific question was to determine if the increases in TH activity after both long-term and short-term increases in neuronal activity occur by the same mechanism.