Regional distribution and control of tyrosine hydroxylase activity in the quail brain

Tyrosine hydroxylase (TH) activity, the rate-limiting step in the synthesis of catecholamines, was quantified in the preoptic area-hypothalamus of adu lt male Japanese quail by a new assay measuring the tritiated water product ion from 3,5-[H-3]-L-tyrosine. Maximal levels of activity were observed at a 20-25 mu M concentration of substrate, with more than 50% inhibition of t he activity being recorded at a 100 mu M concentration. TH activity was lin ear as a function of the incubation time during the first 20 min and maxima l at a pH of 6.0. TH was heterogeneously distributed in the quail brain wit h highest levels of activity being found (in decreasing order) in the mesen cephalon, diencephalon, and telencephalon. Given the large size of the tele ncephalon, this is the brain area that contains, as a whole, the highest le vel of enzyme activity. TH inhibitors that have been well-characterized in mammals, such as 3-iodo-L-tyrosine and L-alpha-methyl-p-tyrosine (AMPT) com pletely inhibited the enzyme activity at a 100 mu M concentration. In mamma ls, the accumulation of catecholamines exerts a negative feedback control o n TH activity. Similar controls were observed in the quail brain. Two inhib itors of the DOPA decarboxylase that should lead to accumulation of DOPA de pressed TH activity by 60% or more, and the inhibitor of the dopamine beta- hydroxylase, fusaric acid that should cause an accumulation of dopamine, su ppressed 90% of the TH activity. The addition of exogenous DOPA, dopamine, or norepinephrine to the brain homogenates also strongly inhibited TH activ ity, independently confirming the feedback effects of the enzyme products o n the enzyme activity. These data demonstrate that TH activity in the quail brain is heterogeneously distributed and acutely regulated, as it is in ma mmals, by the accumulation of its products and of the derived catecholamine s. (C) 1999 Elsevier Science Inc.