Synergistic Action of Postsynaptic α‐Adrenergic Receptor Stimulation on Vasoactive Intestinal Polypeptide‐Induced Increases in Pineal N‐Acetyltransferase Activity

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Abstract
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 .mu.M, 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.