Regulation of chicken pineal arylalkylamine-N-acetyl transferase by postsynaptic alpha 2-adrenergic receptors.
The present investigation sought to characterize the adrenergic inhibition of arylalkylamine-N-acetyltransferase in cultured chicken pineal glands. Arylalkylamine-N-acetyltransferase, the melatonin rhythm generating enzyme, displays daily oscillations of activity that are driven by a circadian oscillator. Norepinephrine released at sympathetic nerve endings inhibits the enzyme and appears to play a role in maintaining a circadian rhythm of melatonin release. Chicken pineal glands were isolated in organ culture and the effects of adrenergic agents on the night time peak of N-acetyltransferase activity were studied. Norepinephrine and clonidine prevented 50 to 65% of the nocturnal rise of N-acetyltransferase activity. When applied at middark, norepinephrine and clonidine caused a 50 to 65% inhibition of N-acetyltransferase activity in 2 hours. Dose-response studies indicated clonidine was 100 times more potent than norepinephrine or cirazoline at inhibiting N-acetyltransferase activity. Inhibition of N-acetyltransferase activity was also observed, at micromolar concentration with epinephrine, UK 14,304 and alpha-methylnorepinephrine but not with phenylephrine, isoproterenol or dopamine. Epinephrine and clonidine actions were antagonized by yohimbine but not by prazosin. Destruction of the presynaptic compartment by bilateral superior cervical ganglionectomy did not affect the clonidine-induced inhibition of N-acetyltransferase and its reversal by yohimbine. It is concluded that the adrenergic inhibition of N-acetyltransferase activity in chicken pineal gland probably occurs via stimulation of postsynaptic alpha 2-adrenergic receptors.
D000123:Acetyltransferases / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002645:Chickens; D002940:Circadian Rhythm; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009924:Organ Culture Techniques; D010870:Pineal Gland / Q000201:enzymology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; D000123:Acetyltransferases; D001191:Arylamine N-Acetyltransferase; D003000:Clonidine; C014282:cirazoline; D009638:Norepinephrine; D004837:Epinephrine