Substance P inhibits the acute stimulation of ganglionic tyrosine hydroxylase activity by a nicotinic agonist.

Incubation of rat superior cervical ganglia with dimethylphenylpiperazinium (30 microM) for 30 min resulted in a two-fold increase in tyrosine hydroxylase activity. This effect was completely inhibited by substance P (30 microM) but not by substance P-free acid, kassinin or physalaemin. Neither of these four peptides alone produced any change in the activity of tyrosine hydroxylase. The IC50 for the inhibitory effect of substance P was approximately 3 microM. Substance P did not inhibit the stimulatory effects of bethanechol or vasoactive intestinal peptide on this enzyme activity. Thus substance P, acting at a site which has a different pharmacology than previously characterized substance P receptors, selectively inhibits nicotinic stimulation of tyrosine hydroxylase activity. These data raise the possibility that substance P may modulate the nicotinic regulation of catecholamine synthesis in sympathetic ganglia in vivo.