期刊
JOURNAL OF BIOLOGICAL RHYTHMS
卷 32, 期 3, 页码 195-211出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/0748730417700458
关键词
N-acetyltryptamine; melatonin; pineal; retina; human; nonhuman primate; daily rhythm; transcriptome profiling
资金
- Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health
- NIH [AG-036670, AG-029612, OD-011092]
- Bert L. and N. Kuggie Vallee Foundation
- WorldQuant Foundation
- NASA [NNX14AH50G, 15-15Omni2-0063]
- Bill and Melinda Gates Foundation [OPP1151054]
- Bill & Melinda Gates Foundation - Grand Challenges Explorations Initiative [OPP1151054] Funding Source: researchfish
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.
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