Synergistic action of postsynaptic alpha-adrenergic receptor stimulation on vasoactive intestinal polypeptide-induced increases in pineal N-acetyltransferase activity.
The alpha-adrenergic agonists phenylephrine and methoxamine, at concentrations that have little effect on pineal N-acetyltransferase activity, markedly enhance stimulation of this enzyme by vasoactive intestinal polypeptide (VIP). This augmentation can be blocked by the alpha 1-adrenergic antagonists phenoxybenzamine and prazosin and, at 10 but not 1 microM, by the alpha 2-antagonist yohimbine. The time course for VIP stimulation is not altered by concomitant alpha-adrenergic stimulation. Augmented activity does not require concomitant alpha-adrenergic stimulation, but alpha-adrenergic agonists must be present for augmentation to be maintained. Phorbol 12,13-diacetate or -dibutyrate but not 4 alpha-phorbol can substitute for phenylephrine, a finding suggesting that protein kinase C is involved in the augmentation. These results are, in general, analogous to alpha-adrenergic magnification of N-acetyltransferase induction by beta-adrenergic agonists.
D000123:Acetyltransferases / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D001262:Atenolol / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010870:Pineal Gland / Q000201:enzymology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D010656:Phenylephrine; D015016:Yohimbine; D014660:Vasoactive Intestinal Peptide; D001262:Atenolol; D011433:Propranolol; D000242:Cyclic AMP; D000123:Acetyltransferases; D001191:Arylamine N-Acetyltransferase; D008729:Methoxamine; D003000:Clonidine; D011224:Prazosin; D010646:Phentolamine