An investigation into the effects of manganese and other divalent cations on tyrosine hydroxylase activity

The activity of tyrosine hydroxylase (TH) was measured in homogenates of hypothalamic tissue and corpus striatum obtained from 24 day old rats. The addition of manganese to the preparations had no direct effect on TH activity in either brain region. Similarly, the addition of calcium, magnesium and lead at concentrations of 1.0 mM did not affect TH activity. Cadmium and zinc (1.0 mM) significantly reduced TH activity in both the hypothalamic area and corpus striatum. Iron (1.0 mM) significantly stimulated TH activity in the corpus striatum but did not affect TH activity in the hypothalamic area. At conentrations of 1.0 mM, neither disodium ethylenediamine tetra-acetic acid (EDTA) nor ethylene glycol bis (beta-amino-ethyl ether)-N,N'-tetraacetic acid (ECTA) affected directly TH activity in either brain region. Cyclic adenosine 3',5'-monophosphate (cAMP) at a concentration of 1.0 mM did not affect TH activity in either the hypothalamic area or corpus striatum. Results from these in vitro studies show clearly that manganese does not inhibit directly TH activity and that manganese does not compete with other physiologically important divalent cations to cause the reduction in TH activity seen in vivo after chronic exposure.