Ethanol enhancement of isoproterenol-stimulated melatonin and cyclic AMP release from cultured pineal glands.
Norepinephrine stimulates the synthesis of melatonin in the pineal gland. The action of norepinephrine is believed to be mediated primarily by beta adrenergic receptors, and involves activation of adenylate cyclase. Ethanol, 25 to 50 mM, added to cultured pineal glands in vitro, enhanced isoproterenol-induced stimulation of cyclic AMP and melatonin production. The action of ethanol was observed only at doses of isoproterenol that produced a submaximal effect, and ethanol alone had no effect on cyclic AMP or melatonin release. Butanol, at a concentration of 2 mM, was as effective as 50 mM ethanol in increasing isoproterenol-stimulated cyclic AMP and melatonin release, indicating that the response to alcohols was not due simply to changes in osmolarity, and may reflect a hydrophobic interaction of the alcohols with the cell membrane. The effects of ethanol on pineal cyclic AMP and melatonin release were reversible after a 15-min preincubation, but not after a 2-hr preincubation, suggesting that, over a long incubation period, ethanol may sensitize the pineal beta adrenergic receptor-coupled adenylate cyclase system to isoproterenol. The findings in this study are consistent with earlier work showing that ethanol increases cerebral cortical beta adrenergic receptor-coupled adenylate cyclase activity, and demonstrate that the effect of ethanol on the receptor-effector system can result in an endocrinological response.
Chung
C T
CT
Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.
Tamarkin
L
L
Hoffman
P L
PL
Tabakoff
B
B
D020001:1-Butanol; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000032:analysis; D000440:Butanols / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D010870:Pineal Gland / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000440:Butanols; D000431:Ethanol; D020001:1-Butanol; D000242:Cyclic AMP; D001191:Arylamine N-Acetyltransferase; D008550:Melatonin; D007545:Isoproterenol