title: Chick pineal clock regulates serotonin N-acetyltransferase mRNA rhythm in culture.
abstract: Melatonin production in the chick pineal gland is high at night and low during the day. This rhythm reflects circadian changes in the activity of serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AA-NAT; EC 2.3.1.87), the penultimate enzyme in melatonin synthesis. In contrast to the external regulation of pineal rhythms in mammals by the suprachiasmatic nucleus, rhythmic changes in AA-NAT activity in cultured chick pineal cells are controlled by an oscillator located in the pineal cells themselves. Here we present evidence that the chick pineal clock generates a rhythm in the abundance of AA-NAT mRNA in cultured cells that parallels the rhythm in AA-NAT activity. In contrast, elevating cAMP by forskolin treatment markedly increases AA-NAT activity without producing strong changes in AA-NAT mRNA levels, and lowering cAMP by norepinephrine treatment decreases enzyme activity without markedly decreasing mRNA. These results suggest that clock-controlled changes in AA-NAT activity occur primarily through changes at the mRNA level, whereas cAMP-controlled changes occur primarily through changes at the protein level. Related studies indicate that the clock-dependent nocturnal increase in AA-NAT mRNA requires gene expression but not de novo protein synthesis, and that AA-NAT mRNA levels are suppressed at all times of the day by a rapidly turning over protein. Further analysis of the regulation of chick pineal AA-NAT mRNA is likely to enhance our understanding of the molecular basis of vertebrate circadian rhythms.
authors.affiliation: Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4480, USA.
authors.forename: M
authors.initials: M
authors.lastname: Bernard
authors.forename: D C
authors.initials: DC
authors.lastname: Klein
authors.forename: M
authors.initials: M
authors.lastname: Zatz
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001191:Arylamine N-Acetyltransferase / Q000096:biosynthesis*; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D002478:Cells, Cultured; D002645:Chickens; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004347:Drug Interactions; D008027:Light; D009638:Norepinephrine / Q000378:metabolism; D010870:Pineal Gland / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis*; D013997:Time Factors
chemical_list: D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D005576:Colforsin; D003513:Cycloheximide; D000242:Cyclic AMP; D001191:Arylamine N-Acetyltransferase; D009638:Norepinephrine