Brain Damage-linked ATP Promotes P2X7 Receptors Mediated Pineal N-acetylserotonin Release

The pineal gland is a key player in surveillance and defense responses. In healthy conditions, nocturnal circulating melatonin (MEL) impairs the rolling and adhesion of leukocytes to the endothelial layer. Fungi, bacteria, and pro-inflammatory cytokines block nocturnal pineal MEL synthesis, facilitating leukocyte migration to injured areas. ATP is a cotransmitter of the noradrenergic signal and potentiates noradrenaline (NAd)-induced MEL synthesis via P2Y(1) receptor (P2Y(1)R) activation. Otherwise, ATP low-affinity P2X7 receptor (P2X7R) activation impairs N-acetylserotonin (NAS) into MEL conversion in NAd incubated pineals. Here we mimicked a focal increase of ATP by injecting low (0.3 and 1.0 mu g) and high (3.0 mu g) ATP in the right lateral ventricle of adult rats. Nocturnal pineal activity mimicked the in culture data. Low ATP doses increased MEL output, while high ATP dose and the P2X7R agonist BzATP (15.0-50.0 ng) increased NAS pineal and blood content. In the brain, the response was structure-dependent. There was an increase in cortical and no change in cerebellar MEL. These effects were mediated by changes in the expression of coding genes to synthetic and metabolizing melatonergic enzymes. Thus, the pineal gland plays a role as a first-line structure to respond to the death of cells inside the brain by turning NAS into the darkness hormone. (C) 2022 IBRO. Published by Elsevier Ltd. All rights reserved.

Automated summary

The pineal gland plays a key role in surveillance and defense responses. Melatonin secreted by the pineal gland regulates the rolling and adhesion of leukocytes. Pathogens and pro-inflammatory cytokines inhibit nocturnal melatonin synthesis, leading to leukocyte migration to injured areas. ATP acts as a cotransmitter and enhances melatonin synthesis. The pineal gland responds differently to different doses of ATP and shows structure-dependent effects in the brain.