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Molecular Pharmacology, Vol 6, 350-356, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

Increased Conversion of Tyrosine to Catecholamines in the Intact Rat Following Elevation of Tissue Tyrosine Hydroxylase Levels by Administered Phenoxybenzamine

WALLACE DAIRMAN 1 and SIDNEY UDENFRIEND 1

1 Roche Institute of Molecular Biology, Nutley, New Jersey 07110

When phenoxybenzamine (20 mg/kg) was administered to rats for 2 consecutive days, a 2-fold increase in tryosine hydroxylase relative to controls was observed in adrenal and heart homogenates. A 4-6-fold increase in the incorporation of label from 14C-L-tyrosine into catecholamines was observed following 2 days of phenoxybenzamine treatment, in comparison to a 2-3-fold increase following a single dose of the alpha-adrenergic blocking agent. The administration of a ganglionic blocking agent 2 hr prior to the administration of 14C-L-tyrosine completely prevented the increased incorporation of label into catecholamines following 1 day of phenoxybenzamine treatment, but caused only a partial reduction in the accelerated rate of conversion of tyrosine to catecholamines observed after 2 days of phenoxybenzamine treatment. These data are consistent with the concept that the increased tyrosine hydroxylase activity measured in tissue homogenates expresses itself physiologically as an acceleration of catecholamine synthesis in the intact animal.

Note:
ACKNOWLEDGMENTS The technical assistance of Mr. Theodore Levine and Mr. James Tarver is gratefully acknowledged. The data on the effect of exercise on rat adrenal tyrosine hydroxylase were obtained by Dr. M. Lipton.

Submitted on January 16, 1970




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