Induction of Tyrosine Hydroxylase in Peripheral and Central Adrenergic Neurones by Cold-exposure of Rats

Abstract

INCREASED utilization of the adrenergic transmitter noradrenaline, resulting from direct nerve stimulation or reflex increase in sympathetic nerve activity, elicits an immediate rise in the synthesis of catecholamines^1–4. It has been suggested that this rapid adaptation is a consequence of decreased end-product inhibition of tyrosine hydroxylase by noradrenaline⁵ or of an increased availability of cofactor or substrate at the enzyme site⁴. No changes in the in vitro tyrosine hydroxylase activity have been detected in these experimental conditions^4,6. It has recently been shown, however, that a drug-induced increase in sympathoadrenal activity provokes not only this immediate, rapid adjustment to the increased activity, but also a long-term adaptation which involves the induction of tyrosine hydroxlyase^7–9, the rate-limiting enzyme in the synthesis of catecholamines¹⁰. Cold-exposure of rats has been found to increase the excretion of catecholamines and their metabolites in urine^11,12 and to enhance the synthesis of noradrenaline in peripheral organs¹³ and specific regions of the central nervous system¹⁴. This study shows that prolonged exposure of rats to cold provokes an increase in the in vitro tyrosine hydroxylase activity not only in peripheral sympathetic ganglia and adrenal medulla, but also in parts of the central nervous system.