N-acetylation of serotonin is correlated with alpha 2- but not with beta-adrenergic regulation of cyclic AMP levels in cultured chick pineal cells.
We investigated the role of cyclic AMP (cAMP) in alpha 2- and possible beta-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 approximately 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 alpha 2-adrenergic potency order of UK 14,304 greater than or equal to clonidine greater than norepinephrine greater than phenylephrine. Noradrenergic inhibition of 3-isobutyl-1-methylxanthine-augmented cAMP levels and NAT activity was reversed by yohimbine (an alpha 2-adrenergic antagonist) but not by prazosin (an alpha 1-adrenergic antagonist). The alpha-adrenergic inhibition of cAMP accumulation and NAT activity was prevented by pertussis toxin. Addition of propranolol (a beta-adrenergic antagonist) was necessary to observe an inhibitory effect of norepinephrine on cAMP levels but not on NAT activity. Similarly, the beta-adrenergic agonist isoproterenol transiently increased cAMP levels but did not affect NAT activity. The data indicate that the alpha 2-adrenergic inhibition of NAT activity in chick pineal cells is strongly correlated with an inhibition of cAMP accumulation. The lack of beta-adrenergic effect on NAT suggests that beta-adrenoceptors might be on a subset of cells that do not produce melatonin or that the beta-adrenergic-induced increase in cAMP levels is too transient to affect NAT.
Voisin
P
P
Laboratoire de Biologie Cellulaire, URA CNRS 290, UFR Sciences, Poitiers, France.
Van Camp
G
G
Collin
J P
JP
D000107:Acetylation; D000818:Animals; D000831:Animals, Newborn; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism; D002645:Chickens; D000242:Cyclic AMP / Q000378:metabolism*; D010870:Pineal Gland / Q000166:cytology / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D012701:Serotonin; D000242:Cyclic AMP; D001191:Arylamine N-Acetyltransferase