Abstract

Monoamine oxidase inhibitors, indirectly acting sympathomimetic amines, reserpine and bretylium, which possess no direct inhibitory effect on tyrosine hydroxylase, inhibit tyrosine hydroxylase in intact, adrenergically innervated tissue, presumably by increasing the concentration of free intraneuronal norepinephrine. The increased free norepinephrine in the axoplasm inhibits tyrosine hydroxylase by competitive antagonism with the pteridine cofactor. The effects of monoamine oxidase inhibitors, indirectly acting sympathomimetic amines, and bretylium on tyrosine hydroxylase can be antagonized by addition of excess pteridine cofactor to the medium. Stimulation of the hypogastric nerve of the isolated vas deferens preparation of the guinea pig is associated with increased tyrosine hydroxylase activity both during stimulation and in the immediate poststimulation period. The poststimulation increase in norepinephrine synthesis is not antagonized by norepinephrine. The increase in tyrosine hydroxylase activity demonstrable during nerve stimulation is partially antagonized by norepinephrine, but is not reversed by the addition of excess reduced pteridine cofactor to the medium.