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Nevertheless, the biotransformation of<jats:styled-content style=\"fixed-case\">NAS<\/jats:styled-content>into melatonin, which occurs due to the subsequent methylation by acetylserotonin O\u2010methyltransferase (<jats:styled-content style=\"fixed-case\">ASMT<\/jats:styled-content>;<jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>2.1.1.4), has not yet been evaluated in the presence of purinergic stimulation. We therefore evaluated the effects of purinergic signaling on melatonin synthesis induced by<jats:italic>\u03b2<\/jats:italic>\u2010adrenergic stimulation.<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>increased<jats:styled-content style=\"fixed-case\">NAS<\/jats:styled-content>levels, but, surprisingly, inhibited melatonin synthesis in an inverse, concentration\u2010dependent manner. Our results demonstrate that enhanced<jats:styled-content style=\"fixed-case\">NAS<\/jats:styled-content>levels, which depend on phospholipase C (<jats:styled-content style=\"fixed-case\">PLC<\/jats:styled-content>) activity (but not the induction of gene transcription), are a post\u2010translational effect. By contrast, melatonin reduction is related to an<jats:styled-content style=\"fixed-case\">ASMT<\/jats:styled-content>inhibition of expression at both the gene transcription and protein levels. These results were independent of nuclear factor\u2010kappa B (<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">kB<\/jats:styled-content>) translocation. Neither the P2Y<jats:sub>1<\/jats:sub>receptor activation nor the<jats:styled-content style=\"fixed-case\">PLC<\/jats:styled-content>\u2010mediated pathway was involved in the decrease in melatonin, indicating that<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>regulates pineal metabolism through different mechanisms. Taken together, our data demonstrate that purinergic signaling differentially modulates<jats:styled-content style=\"fixed-case\">NAS<\/jats:styled-content>and melatonin synthesis and point to a regulatory role for<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>as a cotransmitter in the control of<jats:styled-content style=\"fixed-case\">ASMT<\/jats:styled-content>, the rate\u2010limiting enzyme in melatonin synthesis. The endogenous production of melatonin regulates defense responses; therefore, understanding the mechanisms involving<jats:styled-content style=\"fixed-case\">ASMT<\/jats:styled-content>regulation might provide novel insights into the development and progression of neurological disorders since melatonin presents anti\u2010inflammatory, neuroprotective, and neurogenic effects.<\/jats:p>","DOI":"10.1111\/jpi.12309","type":"journal-article","created":{"date-parts":[[2016,1,6]],"date-time":"2016-01-06T05:58:48Z","timestamp":1452059928000},"page":"242-249","source":"Crossref","is-referenced-by-count":20,"title":["Adenosine triphosphate inhibits melatonin synthesis in the rat pineal gland"],"prefix":"10.1111","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3406-9351","authenticated-orcid":false,"given":"Luis Henrique","family":"Souza\u2010Teodoro","sequence":"first","affiliation":[{"name":"Laboratory of Chronopharmacology Biosciences Institute University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Let\u00edcia","family":"Dargenio\u2010Garcia","sequence":"additional","affiliation":[{"name":"Laboratory of Chronopharmacology Biosciences Institute University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Lopes","family":"Petrilli\u2010Lapa","sequence":"additional","affiliation":[{"name":"Laboratory of Chronopharmacology Biosciences Institute University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewerton da Silva","family":"Souza","sequence":"additional","affiliation":[{"name":"Laboratory of Chronopharmacology Biosciences Institute University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro A. 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