TYROSINE-HYDROXYLASE - DELAYED ACTIVATION IN CENTRAL NORADRENERGIC NEURONS AND INDUCTION IN ADRENAL-MEDULLA ELICITED BY STIMULATION OF CENTRAL CHOLINERGIC RECEPTORS

Abstract

The centrally active muscarinic agonist, oxotremorine, elicited an up to 2-fold dose-dependent (0.25-1.5 mg/kg) increase in the activity of tyrosine hydroxylase (TH) in the rat nucleus locus coeruleus (LC) and adrenal medulla. The response occurred in LC after 24-48 h and in adrenal medulla by 4-8 h, peaked in LC at 72 h and adrenal medulla at 16-24 h and persisted up to 2 wk in both tissues. In brain the effect appeared confined to cell bodies of noradrenergic neurons. The activity of dopamine .beta.-hydroxylase increased in adrenal medulla (40%) but not in brain. Immunotitration with anti-TH serum demonstrated that the increase of TH activity in LC is due to increased catalytic activity (activation), whereas in adrenal medulla it is due to a transynaptically mediated accumulation of enzyme protein (induction). Physostigmine (1.0 mg/kg), pilocarpine (25-50 mg/kg) and nicotine (10 mg/kg) increased TH activity in LC and adrenal. Stimulation of central cholinergic receptors of the muscarinic type appears to result in a delayed and protracted activation of TH but not of dopamine .beta.-hydroxylase in cell bodies of central noradrenergic neurons, and reflexly, to transynaptic induction of TH and dopamine .beta.-hydroxylase in the adrenal medulla.