Molecular Pharmacology, Vol 11, 784-794, Copyright © 1975 by the American Society for Pharmacology and Experimental Therapeutics

Turnover Rate of Tyrosine Hydroxylase during Trans-synaptic Induction

¹ Laboratory of Preclinical Pharmacology, National Institute of Mental Health, Saint Elizabeths Hospital, Washington, D. C. 20032

The tyrosine hydroxylase of adrenal medulla was induced by exposing the rats to 4° for 4 hr. The synthesis rate of normal and induced tyrosine hydroxylase was measured by radiochemical and immunoprecipitation methods. Incorporation of ³H into the enzyme was normal 6 hr after the beginning of the stress but was greater than normal at 10 hr and reached a maximum increase of 65% at 16 hr. Beginning 20 hr after stress application the rate of ³H incorporation declined and approached normal values between 30 and 50 hr. The tyrosine hydroxylase activity was not yet increased 10 hr after the beginning of the stress; however, it was increased at 16 hr and a maximal increment was reached at 24 hr. This new steady state was maintained for the following 24 hr. The enzyme activity then declined, with a half-life of about 3 days. The radioactivity incorporated into tyrosine hydroxylase in glands of normal and stressed rats decayed exponentially, with a half-life of 68 hr. From this first-order rate constant (k_d = 0.01) and from the amount of enzyme present the synthesis rate (K_[unknown]) of tyrosine hydroxylase was calculated. The synthesis rate was increased in the adrenals of stressed rats. This increase failed to occur if adrenal denervation preceded the stress.

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