Calcium signaling and the novel anti-proliferative effect of the UTP-sensitive P2Y11 receptor in rat cardiac myofibroblasts

Cell Calcium
Mariana CertalPaulo Correia-de-Sá

Abstract

During myocardial ischemia and reperfusion both purines and pyrimidines are released into the extracellular milieu, thus creating a signaling wave that propagates to neighboring cells via membrane-bound P2 purinoceptors activation. Cardiac fibroblasts (CF) are important players in heart remodeling, electrophysiological changes and hemodynamic alterations following myocardial infarction. Here, we investigated the role UTP on calcium signaling and proliferation of CF cultured from ventricles of adult rats. Co-expression of discoidin domain receptor 2 and α-smooth muscle actin indicate that cultured CF are activated myofibroblasts. Intracellular calcium ([Ca(2+)]i) signals were monitored in cells loaded with Fluo-4 NW. CF proliferation was evaluated by the MTT assay. UTP and the selective P2Y4 agonist, MRS4062, caused a fast desensitizing [Ca(2+)]i rise originated from thapsigargin-sensitive internal stores, which partially declined to a plateau providing the existence of Ca(2+) in the extracellular fluid. The biphasic [Ca(2+)]i response to UTP was attenuated respectively by P2Y4 blockers, like reactive blue-2 and suramin, and by the P2Y11 antagonist, NF340. UTP and the P2Y2 receptor agonist MRS2768 increased, whereas the selectiv...Continue Reading

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Citations

Feb 20, 2016·Journal of Molecular and Cellular Cardiology·Tatiana NovitskayaRichard J Gumina
Jun 2, 2016·Purinergic Signalling·Karin Dreisig, Birgitte Rahbek Kornum
Aug 26, 2016·Molecular Neurobiology·Luana de Almeida-PereiraLucianne Fragel-Madeira
Jan 13, 2016·Journal of Cellular Physiology·J B Noronha-Matos, P Correia-de-Sá
Aug 16, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Zoubir DjeradaHervé Millart
Oct 11, 2017·Frontiers in Pharmacology·Geoffrey Burnstock
Mar 2, 2018·Experimental Physiology·Noriyuki HatanoWayne R Giles
Jan 19, 2021·Biochemical Pharmacology·Marianna LovásziGyörgy Haskó

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