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.
D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis; D004246:Dimethylphenylpiperazinium Iodide / Q000037:antagonists & inhibitors*; D005728:Ganglia, Sympathetic / Q000201:enzymology* / Q000502:physiology; D066298:In Vitro Techniques; D015286:Kassinin; D009842:Oligopeptides / Q000494:pharmacology; D010803:Physalaemin / Q000494:pharmacology; D010879:Piperazines / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000502:physiology; D013373:Substance P / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D002395:Catecholamines; D009842:Oligopeptides; D010879:Piperazines; D011978:Receptors, Nicotinic; D010803:Physalaemin; D013373:Substance P; D004246:Dimethylphenylpiperazinium Iodide; D004295:Dihydroxyphenylalanine; D015286:Kassinin; D014446:Tyrosine 3-Monooxygenase