Autor(es)

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]

Afiliação do(s) autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: Journal of Pineal Research; v. 60, n. 2, p. 242-249, MAR 2016.
• Citações Web of Science: 5

Resumo

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)

• Processo FAPESP: 12/06110-0 - Efeito da estimulação purinérgica sobre a produção de melatonina por pineais na presença de agentes inflamatórios
• Beneficiário: Leticia Dargenio Garcia
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 07/07871-6 - Eixo Imune-Pineal: produção endócrina e parácrina de melatonina em condições de injúria
• Beneficiário: Regina Pekelmann Markus
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/13691-1 - Eixo imune-pineal: integrando a biologia do tempo em condições fisiológicas, fisiopatológicas e patológicas
• Beneficiário: Regina Pekelmann Markus
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 09/12307-8 - Regulação da atividade da glândula pineal por glicocorticóides mediada por estimulação purinérgica
• Beneficiário: Camila Lopes Petrilli
• Modalidade de apoio: Bolsas no Brasil - Mestrado