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
Date Published2017 Jun

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.

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