Alpha 2-adrenergic regulation of arylalkylamine N-acetyltransferase in organ-cultured chick pineal gland: characterization with agonists and modulation of experimentally stimulated enzyme activity.
In the chicken pineal gland, norepinephrine, released at sympathetic nerve endings, plays a role in synchronizing the circadian rhythm of melatonin synthesis. This effect appears to be exerted via an adrenergic inhibition of arylalkylamine N-acetyltransferase, the melatonin rhythm-generating enzyme. The present study indicates that the nighttime peak of N-acetyltransferase activity developed by organ-cultured chick pineal glands is inhibited by adrenergic agonists with a potency order characterizing alpha 2-adrenergic receptors: UK 14,304 greater than clonidine greater than alpha-methylnorepinephrine = epinephrine greater than cirazoline greater than phenylephrine greater than isoproterenol. The mechanism of this alpha 2-adrenergic response was further analyzed in organ cultures, by studying the ability of clonidine to block the cyclic AMP-dependent and the depolarization-dependent stimulations of N-acetyltransferase activity. Clonidine prevented the rise in N-acetyltransferase activity evoked by the adenylate cyclase activators forskolin and cholera toxin or by the phosphodiesterase inhibitor Ro 20,1724. The stimulatory effect of dibutyryl cyclic AMP was also blocked by clonidine. Activation of pineal alpha 2-adrenergic receptors effectively prevented the stimulation of N-acetyltransferase by depolarizing concentrations of KCl. The possibility that the alpha 2-adrenergic effect might be exerted at a step distal to cyclic AMP production is discussed.
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000123:Acetyltransferases / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002645:Chickens; D002772:Cholera Toxin / Q000494:pharmacology; D002940:Circadian Rhythm / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D009924:Organ Culture Techniques; D010870:Pineal Gland / Q000201:enzymology*; D011189:Potassium Chloride / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D005576:Colforsin; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D003994:Bucladesine; D011189:Potassium Chloride; D002772:Cholera Toxin; D000123:Acetyltransferases; D001191:Arylamine N-Acetyltransferase; D003000:Clonidine