{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:02:23Z","timestamp":1790877743801,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,5,12]],"date-time":"2006-05-12T00:00:00Z","timestamp":1147392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2006,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cannabinoids modulate neuronal and neuroendocrine circuits by binding to cannabinoid receptors acting upon cAMP\/Ca<jats:sup>2+<\/jats:sup>\u2010mediated intracellular signaling cascades. The rat pineal represents an established model to investigate intracellular signaling processes because a well defined input, the neurotransmitter norepinephrine, is transformed via cAMP\/Ca<jats:sup>2+<\/jats:sup>\u2010dependent mechanisms into an easily detectable output signal, the biosynthesis of melatonin. Here we investigated the impact of cannabinoids on norepinephrine\u2010regulated melatonin biosynthesis in the rat pineal. We demonstrated that treatment of cultured rat pineals with 9\u2010carboxy\u201011\u2010nor\u2010delta\u20109\u2010tetrahydrocannabinol (THC), cannabidiol or cannabinol significantly reduced norepinephrine\u2010induced arylalkylamine <jats:italic>N<\/jats:italic>\u2010acetyltransferase (AANAT) activity and melatonin biosynthesis. These effects were not mimicked by the cannabinoid receptor agonist WIN55,212\u20132 and were not blocked by cannabinoid 1 and 2 receptor antagonists. The cannabinoids used did not affect norepinephrine\u2010induced increases in cAMP\/Ca<jats:sup>2+<\/jats:sup> levels. Notably, cannabinoids were found to directly inhibit AANAT activity in lysates of the pineal gland. This effect was specific in so far as cannabinoids did not influence the activity of hydroxyindole\u2010<jats:italic>O<\/jats:italic>\u2010methyltransferase (HIOMT), the last enzyme in melatonin biosynthesis. Taken together, our data strongly suggest that cannabinoids inhibit AANAT activity and attenuate melatonin biosynthesis through intracellular actions without involvement of classical cannabinoid receptor\u2010dependent signaling cascades.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2006.03873.x","type":"journal-article","created":{"date-parts":[[2006,5,12]],"date-time":"2006-05-12T12:30:01Z","timestamp":1147437001000},"page":"267-278","source":"Crossref","is-referenced-by-count":24,"title":["Cannabinoids attenuate norepinephrine\u2010induced melatonin biosynthesis in the rat pineal gland by reducing arylalkylamine <i>N<\/i>\u2010acetyltransferase activity without involvement of cannabinoid receptors"],"prefix":"10.1111","volume":"98","author":[{"given":"Marco","family":"Koch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faramarz","family":"Dehghani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Habazettl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof","family":"Schomerus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horst\u2010Werner","family":"Korf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,5,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(92)90474-N"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/378783a0"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.60.1.155"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.04.053"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb14321.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490110107"},{"key":"e_1_2_7_9_1","first-page":"27","article-title":"Cannabinoid receptors: G\u2010protein\u2010mediated signal transduction mechanisms","volume":"59","author":"Childers S. 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