Daily Rhythm in Plasma N-acetyltryptamine

Peter S. Backlund, Henryk F. Urbanski, Mark A. Doll, David W. Hein, Marjan Bozinoski, Christopher E. Mason, Steven L. Coon, David C. Klein

    Research output: Contribution to journalArticlepeer-review

    13 Scopus citations


    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.

    Original languageEnglish (US)
    Pages (from-to)195-211
    Number of pages17
    JournalJournal of biological rhythms
    Issue number3
    StatePublished - Jun 1 2017


    • N-acetyltryptamine
    • daily rhythm
    • human
    • melatonin
    • nonhuman primate
    • pineal
    • retina
    • transcriptome profiling

    ASJC Scopus subject areas

    • Physiology
    • Physiology (medical)


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