Activation of Tyrosine Hydroxylase in the Superior Cervical Ganglion by Nicotinic and Muscarinic Agonists

Abstract

Both dimethylphenylpiperazinium (DMPP), a nicotinic agonist, and bethanechol, a muscarinic agonist, increase dopa synthesis in the superior cervical ganglion of the rat, DMPP causes an .apprx. 5-fold increase in dopa accumulation in intact ganglia; bethanechol causes an .apprx. 2-fold increase in dopa accumulation. These effects are additive with each other and with the increase in dopa accumulation produced by 8-bromo cAMP. The action of DMPP is dependent on extracellular Ca2+, while the actions of bethanechol and 8-bromo cAMP are not dependent on extracellular Ca2+. Cholinergic agonists and cyclic nucleotides produce a stable activation of tyrosine hydroxylase (TH) in the ganglion. The activation of TH by nicotinic and muscarinic agonists can be detected after 5 min of incubation of the ganglia with these agents. The nicotinic response disappears after 30 min of incubation; the muscarinic response persists for at least 30 min. The Ca2+ dependence of the TH activation produced by these agents is similar to the Ca2+ dependence of their effects on dopa accumulation in intact ganglia. These data are consistent with the hypothesis that nicotinic agonists, muscarinic agonists and cAMP analogs increase TH activity by 3 distinct mechanisms. The activation of TH presumably underlies the increases in dopa synthesis produced by these agents.