ACCELERATION OF CATECHOLAMINE FORMATION IN THE GUINEA-PIG VAS DEFERENS AFTER HYPOGASTRIC NERVE STIMULATION: ROLES OF TYROSINE HYDROXYLASE AND NEW PROTEIN SYNTHESIS

¹ Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland; Department of Pharmacology, University of Colorado School of Medicine, Denver, Colorado

Stimulation of the hypogastric nerve vas deferens preparation in vitro is associated with increased formation of dopamine and norepinephrine from labeled tyrosine both during and after stimulation. After stimulation for one hour, no changes in tyrosine-¹⁴C uptake or endogenous tyrosine and norepinephrine levels are observed. Tyrosine hydroxylase activity of homogenates prepared from these stimulated vasa deferentia is unaltered. The increased activity of tyrosine hydroxylase in intact vas deferens after nerve stimulation does not seem to be related to increased availability of pterin co-factor since excess 6,7-dimethyltetrahydropterine does not abolish the effect. Puromycin decreases the formation of catecholamines from tyrosine in intact vasa deferentia and inhibits the increased synthesis associated with previous nerve stimulation, but does not affect tyrosine hydroxylase activity in homogenates prepared from this tissue. Furthermore, the effect of puromycin on norepinephrine synthesis is not a consequence of inhibition of protein synthesis or of any other general property of inhibitors of protein synthesis since neither cycloheximide, in doses which produce a comparable decrease in protein synthesis, nor actinomycin decreases norepinephrine synthesis. These results suggest that the augmented synthesis of catecholamines which occurs in sympathetic nerves after short-term stimulation is not the result of any change in the level of tyrosine hydroxylase or pterin co-factor. It is suggested that since puromycin contains a p-methoxytyrosine residue, it may produce its inhibition of catecholamine synthesis by interfering with tyrosine-¹⁴C entry into sympathetic nerve cells.