Agomelatine inhibits platelet aggregation through melatonin receptor-dependent and independent mechanisms

Autor(es)

Vicente, Julia Modesto ; Lescano, Caroline Honaiser ; Bordin, Silvana ; Monica, Fabiola Zakia ; Gobbi, Gabriella ; Anhe, Gabriel Forato

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 328, p. 14-pg., 2023-09-01.

Resumo

Aims: Melatonin is known to inhibit platelet aggregation induced by arachidonic acid (AA). In the present study we investigated whether agomelatine (Ago), an antidepressant with agonist activity at melatonin receptor 1 (MT1) and MT2 could reduce platelets aggregation and adhesion.Main methods: Human platelets from healthy donors were used to test the in vitro effects of Ago in the presence of different platelet activators. We performed aggregation and adhesion assays, thromboxane B2 (TxB2), cAMP and cGMP measurements, intra-platelet calcium registration and flow cytometry assays.Key findings: Our data revealed that different concentrations of Ago reduced AA-and collagen-induced human platelet aggregation in vitro. Ago also reduced AA-induced increase in thromboxane B2 (TxB2) production, intracellular calcium levels and P-selectin expression at plasma membrane. The effects of Ago in AA-activated platelets were likely dependent on MT1 as they were blocked by luzindole (a MT1/MT2 antagonist) and mimicked by the MT1 agonist UCM871 in a luzindole-sensitive manner. The MT2 agonist UCM924 was also able to inhibit platelet aggregation, but this response was not affected by luzindole. On the other hand, although UCM871 and UCM924 reduced collagen-induced platelet aggregation and adhesion, inhibition of collagen-induced platelet aggregation by Ago was not mediated by melatonin receptors because it was not affected by luzindole.Significance: The present data show that Ago suppresses human platelet aggregation and suggest that this anti-depressant may have the potential to prevent atherothrombotic ischemic events by reducing thrombus formation and vessel occlusion. (AU)

• Processo FAPESP: 19/03196-0 - Mecanismos moleculares envolvidos na inflexibilidade metabólica de ratos submetidos à programação fetal por excesso de glicocorticoides
• Beneficiário: Silvana Auxiliadora Bordin da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/07607-8 - CMPO - Centro Multidisciplinar de Pesquisa em Obesidade e Doenças Associadas
• Beneficiário: Licio Augusto Velloso
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 19/19488-0 - Estudo do efeito da agomelatina na agregação e adesão em plaquetas humanas
• Beneficiário: Julia Modesto Vicente
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 20/13940-5 - Impactos da história transitória de obesidade em diferentes momentos da vida sobre a inflamação pulmonar alérgica
• Beneficiário: Gabriel Forato Anhê
• Modalidade de apoio: Auxílio à Pesquisa - Regular