Adenosine triphosphate inhibits melatonin synthesis in the rat pineal gland

Author(s)

Souza-Teodoro, Luis Henrique ^[1] ; Dargenio-Garcia, Leticia ^[1] ; Petrilli-Lapa, Camila Lopes ^[1] ; Souza, Ewerton da Silva ^[1] ; Fernandes, Pedro A. C. M. ^[1] ; Markus, Regina P. ^[1] ; Ferreira, Zulma S. ^[1]

Affiliation

^[1] Univ Sao Paulo, Biosci Inst, Lab Chronopharmacol, Sao Paulo - Brazil

• Document type: Journal article
• Source: Journal of Pineal Research; v. 60, n. 2, p. 242-249, MAR 2016.
• Web of Science Citations: 5

Abstract

Adenosine triphosphate (ATP) is released onto the pinealocyte, along with noradrenaline, from sympathetic neurons and triggers P2Y(1) receptors that enhance -adrenergic-induced N-acetylserotonin (NAS) synthesis. Nevertheless, the biotransformation of NAS into melatonin, which occurs due to the subsequent methylation by acetylserotonin O-methyltransferase (ASMT; EC 2.1.1.4), has not yet been evaluated in the presence of purinergic stimulation. We therefore evaluated the effects of purinergic signaling on melatonin synthesis induced by -adrenergic stimulation. ATP increased NAS levels, but, surprisingly, inhibited melatonin synthesis in an inverse, concentration-dependent manner. Our results demonstrate that enhanced NAS levels, which depend on phospholipase C (PLC) activity (but not the induction of gene transcription), are a post-translational effect. By contrast, melatonin reduction is related to an ASMT inhibition of expression at both the gene transcription and protein levels. These results were independent of nuclear factor-kappa B (NF-kB) translocation. Neither the P2Y(1) receptor activation nor the PLC-mediated pathway was involved in the decrease in melatonin, indicating that ATP regulates pineal metabolism through different mechanisms. Taken together, our data demonstrate that purinergic signaling differentially modulates NAS and melatonin synthesis and point to a regulatory role for ATP as a cotransmitter in the control of ASMT, the rate-limiting enzyme in melatonin synthesis. The endogenous production of melatonin regulates defense responses; therefore, understanding the mechanisms involving ASMT regulation might provide novel insights into the development and progression of neurological disorders since melatonin presents anti-inflammatory, neuroprotective, and neurogenic effects. (AU)

• FAPESP's process: 12/06110-0 - Effect of purinergic stimulation on the pineal melatonin production by the presence of inflammatory agents
• Grantee: Leticia Dargenio Garcia
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 07/07871-6 - Imune-pineal Axis: injury shifts melatonin production from endocrine to paracrine
• Grantee: Regina Pekelmann Markus
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/13691-1 - Immune-pineal axis: time-niology integrated to surveillance and defense
• Grantee: Regina Pekelmann Markus
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 09/12307-8 - Regulation of the pineal gland activity by glucocorticoids mediated by purinergic stimulation
• Grantee: Camila Lopes Petrilli
• Support Opportunities: Scholarships in Brazil - Master