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Journal of biological rhythms
06, 2017;32 (3): 195-211.

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
Author Information
  1. Peter S Backlund: Biomedical Mass Spectrometry Facility, Intramural Research Program.
  2. Henryk F Urbanski: Divisions of Neuroscience.
  3. Mark A Doll: Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.
  4. David W Hein: Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.
  5. Marjan Bozinoski: Department of Physiology and Biophysics.
  6. Christopher E Mason: Department of Physiology and Biophysics.
  7. Steven L Coon: Section on Neuroendocrinology, Program in Developmental Endocrinology and Genetics.
  8. David C Klein: Section on Neuroendocrinology, Program in Developmental Endocrinology and Genetics.
PMID: 28466676 DOI: 10.1177/0748730417700458

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.

Keywords

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

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Grants

  1. R56 AG029612/NIA NIH HHS
  2. R01 AG029612/NIA NIH HHS
  3. ZIC HD001421-16/Intramural NIH HHS
  4. P51 OD011092/NIH HHS
  5. R01 AG036670/NIA NIH HHS

MeSH Term

Animals
Arylalkylamine N-Acetyltransferase
Circadian Rhythm
Gene Expression Profiling
Humans
Macaca mulatta
Male
Melatonin
Photoperiod
Pineal Gland
Rats
Retina
Tandem Mass Spectrometry
Tryptamines

Chemicals

Tryptamines
N-acetyltryptamine
Arylalkylamine N-Acetyltransferase
Melatonin
Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, N.I.H., Intramural

Links to CNCB-NGDC Resources

GEN: GEND000611 (Next Generation Sequencing Study of Circadian Changes in Transcriptome of Rhesus Macaque Pineal Gland and Retina)

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