Synergistic effects of muscarinic agonists and secretin or vasoactive intestinal peptide on the regulation of tyrosine hydroxylase activity in sympathetic neurons.
Cholinergic agonists and certain peptides of the glucagon-secretin family acutely increase tyrosine hydroxylase activity in the superior cervical ganglion in vitro. The present study was designed to investigate possible interactions between these two classes of agonists in regulating catecholamine biosynthesis. Synergistic effects were found between carbachol and either secretin or vasoactive intestinal peptide in the regulation of DOPA (dihydroxyphenylalanine) synthesis. In addition, synergism was found at the level of the accumulation of cyclic adenosine monophosphate, the likely second messenger in the peptidergic regulation of tyrosine hydroxylase activity. The synergism seen with carbachol was blocked by a muscarinic, but not by a nicotinic, antagonist. Synergism was also found between bethanechol, a muscarinic agonist, and secretin, but not between secretin and dimethylphenylpiperazinium, a nicotinic agonist. Since previous immunohistochemical results suggest that vasoactive intestinal peptide and acetylcholine are colocalized in some preganglionic sympathetic neurons, the present data raise the possibility that the two might act synergistically in vivo in regulating catecholamine biosynthesis. Synergistic postsynaptic actions may be a common feature at synapses where peptides of the secretin-glucagon and acetylcholine are colocalized.
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Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
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D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis / Q000187:drug effects*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004357:Drug Synergism; D005731:Ganglionic Stimulants / Q000494:pharmacology; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012633:Secretin / Q000494:pharmacology*; D017783:Superior Cervical Ganglion / Q000187:drug effects* / Q000201:enzymology; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects* / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D005731:Ganglionic Stimulants; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D018723:Bethanechol; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D004246:Dimethylphenylpiperazinium Iodide; D004295:Dihydroxyphenylalanine; D002217:Carbachol; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase