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Melatonin is accepted as a hormone of night. Could NAS and NAT serve that role too? Methods: Concentration\u2010response measurements with overexpressed human melatonin receptors MT<jats:sub>1<\/jats:sub> and MT<jats:sub>2<\/jats:sub>; mass spectrometry analysis of norepinephrine\u2010stimulated secretions from isolated rat pineal glands; analysis of 24\u2010hour periodic samples of rat blood. Results: We show that NAT and NAS do activate melatonin receptors MT<jats:sub>1<\/jats:sub> and MT<jats:sub>2<\/jats:sub>, although with lower potency than melatonin, and that in vitro, melatonin and NAS are secreted from stimulated, isolated pineal glands in roughly equimolar amounts, but secretion of NAT was much less. All three were found at roughly equal concentrations in blood during the night. However, during the day, serum melatonin fell to very low values creating a high\u2010amplitude circadian rhythm that was absent after pinealectomy, whereas NAS and NAT showed only small or no circadian variation. Conclusion: Blood levels of NAS and NAT were insufficient to activate peripheral melatonin receptors, and they were invariant, so they could not serve as circulating hormones of night. However, they could instead act in paracrine circadian fashion near the pineal gland or via other higher\u2010affinity receptors.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jpi.12622","type":"journal-article","created":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T19:39:55Z","timestamp":1573587595000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Two indoleamines are secreted from rat pineal gland at night and act on melatonin receptors but are not night hormones"],"prefix":"10.1111","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2652-8797","authenticated-orcid":false,"given":"Bo Hyun","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics University of Washington School of Medicine Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4721-763X","authenticated-orcid":false,"given":"Ivana 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Washington School of Medicine Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7266-1671","authenticated-orcid":false,"given":"Bertil","family":"Hille","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics University of Washington School of Medicine Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,12,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.69.6.1583"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(72)90054-6"},{"issue":"25","key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"11608","DOI":"10.1016\/S0021-9258(18)67286-2","article-title":"Essential role of calcium influx in the adrenergic regulation of cAMP and cGMP in rat pinealocytes","volume":"261","author":"Sugden AL","year":"1986","journal-title":"J Biol 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