Daily Rhythm in Plasma N-acetyltryptamine

作者：Backlund Peter S; Urbanski Henryk F; Doll Mark A; Hein David W; Bozinoski Marjan; Mason Christopher E; Coon Steven L; Klein David C^*

来源：Journal of Biological Rhythms, 2017, 32(3): 195-211.

DOI：10.1177/0748730417700458

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

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.

• 出版日期2017-6