Abstract

Electrical nerve stimulation of the isolated hypogastric nerve-vas deferens preparation of the guinea-pig is associated with increased formation of H³-norepinephrine from H³-tyrosine. The effect is similar in the presence or absence of pargyline, a monoamine oxidase inhibitor. In contrast, nerve stimulation is not associated with a significant increase in the synthesis of H³-norepinephrine from H³-dihydroxyphenylalanine. The uptake of H³-tyrosine and its incorporation into tissue protein is not affected by nerve stimulation. The tissue content of norepinephrine and the metabolism of exogenous labeled norepinephrine are identical in stimulated and control preparations. Norepinephrine inhibits the synthesis of H³-norepinephrine from H³-tyrosine and blocks the accelerated synthesis of norepinephrine which is ordinarily seen during nerve stimulation. Pargyline slightly potentiates this inhibitory effect of norepinephrine. The results indicate that a relatively small pool of intraneuronal norepinephrine which is able to interact with tyrosine hydroxylase inhibits this enzyme and thus regulates its own synthesis by a feedback inhibition mechanism. It is proposed that nerve stimulation leads to a reduction in the concentration of that norepinephrine which can interact with the tyrosine hydroxylase. This results in activation of the normally inhibited enzyme and consequent acceleration of norepinephrine synthesis.