{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T05:41:45Z","timestamp":1697175705894},"reference-count":43,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2004,7,30]],"date-time":"2004-07-30T00:00:00Z","timestamp":1091145600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2004,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In all mammalian species investigated, noradrenaline activates a \u03b2\u2010adrenoceptor\/cAMP\/protein kinase A\u2010dependent mechanism to switch on arylalkylamine <jats:italic>N<\/jats:italic>\u2010acetyltransferase and melatonin biosynthesis in the pineal gland. Other compounds which are known to influence the melatonin\u2010generating system are phorbol esters. The effect of phorbol esters on regulation of melatonin synthesis has been mainly investigated in rat pinealocytes. In these cells, phorbol esters do not increase cAMP levels and arylalkylamine <jats:italic>N<\/jats:italic>\u2010acetyltransferase on their own; however, phorbol esters potentiate the effects on cAMP and AANAT activity induced upon \u03b2\u2010adrenoceptor stimulation. In the present study, we investigated the effect of phorbol esters on the regulation of melatonin synthesis in bovine pinealocytes. We show that, in these cells, the phorbol esters 4\u03b2\u2010phorbol 12\u2010myristate 13\u2010acetate (PMA) or phorbol 12,13\u2010dibutyrate have a direct stimulatory effect and induced 4\u201310\u2010fold increases in AANAT protein levels, AANAT activity and melatonin production. The extent of these effects was similar to those induced by noradrenaline. Notably, responses to PMA were not accompanied by increases in cAMP levels. Northern blot analysis showed that <jats:italic>Aanat<\/jats:italic> mRNA levels did not change upon PMA treatment indicating that phorbol esters control AANAT at a post\u2010transcriptional level. The effects on AANAT and melatonin production were reduced by use of protein kinase C inhibitors, but not by blockade of the cyclic AMP\/protein kinase A pathway. Our results point towards a novel mechanism in the regulation of melatonin production that is cAMP\u2010independent and involves protein kinase C. The study is of particular interest because regulation of melatonin biosynthesis in bovines may resemble that in primates more closely than that in rodents.<\/jats:p>","DOI":"10.1111\/j.1365-2826.2004.01228.x","type":"journal-article","created":{"date-parts":[[2004,9,3]],"date-time":"2004-09-03T09:22:59Z","timestamp":1094203379000},"page":"741-749","source":"Crossref","is-referenced-by-count":6,"title":["Activation of Arylalkylamine <i>N<\/i>\u2010Acetyltransferase by Phorbol Esters in Bovine Pinealocytes Suggests a Novel Regulatory Pathway in Melatonin 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