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Daily Rhythm in Plasma N-acetyltryptamine.

TitleDaily Rhythm in Plasma N-acetyltryptamine.
Publication TypeJournal Article
Year of Publication2017
AuthorsBacklund PS, Urbanski HF, Doll MA, Hein DW, Bozinoski M, Mason CE, Coon SL, Klein DC
JournalJ Biol Rhythms
Volume32
Issue3
Pagination195-211
Date Published2017 Jun
ISSN1552-4531
Abstract

Normal physiology undergoes 24-h changes in function that include daily rhythms in circulating hormones, most notably melatonin and cortical steroids. This study focused on N-acetyltryptamine, a little-studied melatonin receptor mixed agonist-antagonist and the likely evolutionary precursor of melatonin. The central issue addressed was whether N-acetyltryptamine is physiologically present in the circulation. N-acetyltryptamine was detected by LC-MS/MS in daytime plasma of 3 different mammals in subnanomolar levels (mean ± SEM: rat, 0.29 ± 0.05 nM, n = 5; rhesus macaque, 0.54 ± 0.24 nM, n = 4; human, 0.03 ± 0.01 nM, n = 32). Analysis of 24-h blood collections from rhesus macaques revealed a nocturnal increase in plasma N-acetyltryptamine (p < 0.001), which varied from 2- to 15-fold over daytime levels among the 4 animals studied. Related RNA sequencing studies indicated that the transcript encoding the tryptamine acetylating enzyme arylalkylamine N-acetyltransferase (AANAT) is expressed at similar levels in the rhesus pineal gland and retina, thereby indicating that either tissue could contribute to circulating N-acetyltryptamine. The evidence that N-acetyltryptamine is a physiological component of mammalian blood and exhibits a daily rhythm, together with known effects as a melatonin receptor mixed agonist-antagonist, shifts the status of N-acetyltryptamine from pharmacological tool to candidate for a physiological role. This provides a new opportunity to extend our understanding of 24-h biology.

DOI10.1177/0748730417700458
Alternate JournalJ. Biol. Rhythms
PubMed ID28466676
PubMed Central IDPMC5571864
Grant ListP51 OD011092 / OD / NIH HHS / United States
ZIC HD001421-16 / / Intramural NIH HHS / United States