Neuromedin U potentiates ADP- and epinephrine-induced human platelet activation

Thrombosis Research
C GrippiC Cerletti

Abstract

Neuromedin U (NmU) is a pleiotropic hypothalamic neuropeptide involved in the gut-brain axis. It acts via both a Gαq/11-coupled receptor (NMUR1) and a Gαi-coupled receptor (NMUR2) in different cell types. Expression of both receptors was reported in platelets, but their significance for NmU signaling remains elusive. We studied the potential effects of NmU on human platelet activation. In platelet-rich plasma (PRP), NmU alone (up to 10μM) did not induce any measurable aggregation, but at nanomolar concentrations, it potentiated platelet aggregation by low (mean 0.47μM) ADP concentrations (from 25.9±3.6% to 74.8±2.7% maximal aggregation for ADP vs. ADP+NmU, 100nM, mean±SEM, n=13), accompanied by platelet P-selectin expression and intracellular calcium mobilization. Accordingly, platelet preincubation with NmU for 2min sensitized platelets for subsequent activation by ADP. When P2Y1 was inactivated by 50μM MRS2179, NmU comparably potentiated ADP-induced PRP aggregation, suggestive of cooperative activation with Gαi-coupled P2Y12. Likewise, NmU potentiated platelet aggregation by Gαi-operated epinephrine at subthreshold concentrations (99ng/ml, mean), but not that by Gαq-dependent serotonin (20μM). Platelet aggregation by NmU/epin...Continue Reading

Citations

Jan 5, 2021·Epigenetics : Official Journal of the DNA Methylation Society·Annalisa MarottaFrancesco Gianfagna
Sep 6, 2020·Immunology·Yuan YeLuzheng Xue
Sep 19, 2019·Current Medicinal Chemistry·An De PrinsSteven Ballet

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