Daily Rhythm in Plasma N-acetyltryptamine.

Area of Science:

• Chronobiology
• Endocrinology
• Biochemistry

Background:

• Normal physiology exhibits 24-hour variations in hormone levels, including melatonin and cortical steroids.
• N-acetyltryptamine, a melatonin receptor agonist-antagonist, is a potential evolutionary precursor to melatonin.
• The physiological presence and role of N-acetyltryptamine in circulation remain largely uncharacterized.

Purpose of the Study:

• To determine if N-acetyltryptamine is physiologically present in mammalian circulation.
• To investigate the daily rhythmicity of N-acetyltryptamine in plasma.
• To explore potential sources of circulating N-acetyltryptamine.

Main Methods:

• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to detect and quantify N-acetyltryptamine in plasma.
• 24-hour blood collections were performed on rhesus macaques to analyze plasma N-acetyltryptamine levels over a day.
• RNA sequencing was employed to assess the expression of arylalkylamine N-acetyltransferase (AANAT) in the pineal gland and retina.

Main Results:

• N-acetyltryptamine was detected at subnanomolar levels in the daytime plasma of rats, rhesus macaques, and humans.
• Plasma N-acetyltryptamine levels in rhesus macaques exhibited a significant nocturnal increase, varying 2- to 15-fold over daytime levels.
• Arylalkylamine N-acetyltransferase (AANAT) transcript expression was found in both the rhesus pineal gland and retina, suggesting these tissues as potential sources.

Conclusions:

• N-acetyltryptamine is a physiological component of mammalian blood.
• Circulating N-acetyltryptamine demonstrates a daily rhythm, similar to other key hormones.
• These findings reposition N-acetyltryptamine from a pharmacological agent to a candidate molecule with a physiological role in 24-hour biology.