Modulation of rat pineal acetyl-Co A:arylamine N-acetyltransferase induction by alpha adrenergic drugs.
The modulatory effects of alpha adrenergic drugs on the induction of rat pineal acetyl-CoA:arylamine N-acetyltransferase (NAT) activity were characterized using both in vivo and organ culture techniques. Intraperitoneal administration of phenoxybenzamine (POB) to rats was followed by a 2- to 3-fold increase in activity of pineal NAT, an enzyme involved in the biosynthesis of the putative pineal hormone melatonin. The increase was greater than 60-fold when POB was administered to ganglionectomized rats. NAT induction after POB administration to ganglionectomized rats was not influenced by adrenalectomy, suggesting that the response to POB was not mediated through the release of catecholamines from adrenomedullary catecholamine stores. To determine whether the pharmacologic site of the activity of POB was located within the pineal body itself, pineals were incubated with POB in organ culture. Significant induction of pineal NAT was not observed when pineals were cultured with POB alone. However, POB shifted the dose-response curve for NAT induction by norepinephrine (NE) to the left. Modulation of NAT induction by POB in organ culture was blocked by dl-propranolol HCl, suggesting that such modulation is mediated through a beta adrenergic mechanism. POB did not modulate NE-mediated NAT induction in pineals extracted from superior cervical ganglionectomized rats. Similarly, the modulatory response to POB was eliminated by 24-hr preincubation in culture medium. These results suggest that elements that are disrupted after ganglionectomy or during a period of preincubation are vital for expression of the modulatory activity of POB.(ABSTRACT TRUNCATED AT 250 WORDS)
D000123:Acetyltransferases / Q000096:biosynthesis*; D000315:Adrenalectomy; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005724:Ganglia / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D009924:Organ Culture Techniques; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010870:Pineal Gland / Q000187:drug effects / Q000201:enzymology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010656:Phenylephrine; D011433:Propranolol; D000123:Acetyltransferases; D001191:Arylamine N-Acetyltransferase; D009638:Norepinephrine; D010646:Phentolamine