N-ACETYLATION OF SEROTONIN IS CORRELATED WITH ALPHA-2-ADRENERGIC BUT NOT WITH BETA-ADRENERGIC REGULATION OF CYCLIC-AMP LEVELS IN CULTURED CHICK PINEAL CELLS

Abstract: We investigated the role of cyclic AMP (cAMP) in α2‐ and possible β‐adrenergic regulation of arylalkylamine‐N‐acetyltransferase (NAT), the penultimate enzyme in the biosynthesis of melatonin. The study was performed on primary cultures of dispersed chick pineal cells. Electron microscopy indicated that ∼70% of the dispersed cells were modified photoreceptors. A similar proportion of melatoninergic cells was detected by immunocytochemical labeling of hydroxyindole‐O‐methyltransferase, the final enzyme in the biosynthesis of melatonin. Adrenergic agonists caused a sustained 50% inhibition of forskolin‐augmented cAMP levels and NAT activity, with an α2‐adrenergic potency order of UK 14,304 clonidine > norepinephrine > phenylephrine. Noradrenergic inhibition of 3‐isobutyl‐1‐methylxanthine‐augmented cAMP levels and NAT activity was reversed by yohimbine (an α2‐adrenergic antagonist) but not by prazosin (an α1‐adrenergic antagonist). The α2‐adrenergic inhibition of cAMP accumulation and NAT activity was prevented by pertussis toxin. Addition of propranolol (a β‐adrenergic antagonist) was necessary to observe an inhibitory effect of norepinephrine on cAMP levels but not on NAT activity. Similarly, the β‐adrenergic agonist isoproterenol transiently increased cAMP levels but did not affect NAT activity. The data indicate that the α2‐adrenergic inhibition of NAT activity in chick pineal cells is strongly correlated with an inhibition of cAMP accumulation. The lack of β‐adrenergic effect on NAT suggests that β‐adrenoceptors might be on a subset of cells that do not produce melatonin or that the β‐adrenergic‐induced increase in cAMP levels is too transient to affect NAT. Copyright © 1990, Wiley Blackwell. All rights reserved