Biochemical Regulation of the Response of the Sympathetic Nervous System

摘要

This project has examined molecular mechanisms regulating the reactivity of the adrenal medulla and sympathetic nervous system. The isolated perfused rat adrenal gland preparation was established in this laboratory to evaluate the effects of physiological and environmental manipulation on the responsivity of the adrenal medulla. Treatments, such as chronic immobilization or cold stress, which result in prolonged adrenal medullary discharge in vivo, result in enhanced adrenal medullary reactivity in vitro as evidenced by the increased secretion of epinephrine from the perfused adrenal gland. The specific biochemical processes underlying this increased reactivity are being investigated using tyrosine hydroxylase, the rate limiting enzyme in the synthesis of the catecholamine neurotransmitters, as a key marker protein. Tyrosine hydroxylase is known to be phosphorylated by four distinct protein kinases in up to four unique sites. The activity of this protein is correlated with tissue levels of catecholamines and its induction is correlated with the enhancement of the bioreactivity of the perfused adrenal gland. Factors that modulate tissue levels of catecholamines and tyrosine hydroxylase are being investigated to determine the mechanism by which they modulate the amount of catecholamines released in response to a fixed dose of acetylcholine.