Functional and molecular evidence for heteromeric association of P2Y(1) receptor with P2Y(2) and P2Y(4) receptors in mouse granulocytes

Functional and molecular evidence for heteromeric association of P2Y(1) receptor with P2Y(2) and P2Y(4) receptors in mouse granulocytes

Author Ribeiro-Filho, Antonio Carlos Google Scholar
Buri, Marcus Vinicius Autor UNIFESP Google Scholar
Barros, Carlos Castilho Google Scholar
Dreyfuss, Juliana Luporini Autor UNIFESP Google Scholar
Nader, Helena Bonciani Autor UNIFESP Google Scholar
Justo, Giselle Zenker Autor UNIFESP Google Scholar
Craveiro, Rogerio Bastos Autor UNIFESP Google Scholar
Pesquero, Joao Bosco Autor UNIFESP Google Scholar
Miranda, Antonio Autor UNIFESP Google Scholar
Ferreira, Alice Teixeira Autor UNIFESP Google Scholar
Paredes-Gamero, Edgar Julian Autor UNIFESP Google Scholar
Abstract Background: All hematopoietic cells express P2 receptors, however pharmacological characteristics such as expression and affinity in granulocytes are unknown. Methods: Pharmacological characteristics of P2 receptors were evaluated by Ca2+ measurements using Fura-2 fluorophore. P2 receptors expression were analyzed by flow cytometry and RT-PCR. P2 interaction were shown by coimmunoprecipitation, western blotting and FRET. Results: Granulocytes were responsive to P2Y agonists, whereas P2X agonists were ineffective. Ca2+ increase, elicited by ADP and UTP was dependent on intracellular stocks and sensitive to G-coupled receptor inhibition. Moreover, MRS2179, a specific antagonist of the P2Y(1) receptor, abolished ADP response. Interestingly, ADP and UTP exhibited full heterologous desensitization, suggesting that these agonists interact with the same receptor. The heteromeric association between P2Y(1) receptor and the P2Y(2) and P2Y(4) receptors was shown by immunoprecipitation and FRET analysis. Conclusion: Clear evidence of heteromeric association of P2Y receptors was found during the evaluation of P2 receptors present in mice granulocytes, which could impact in the classical pharmacology of P2Y receptors in granulocytes.
Keywords P2Y receptors
Calcium signaling
Heteromeric association
Granulocytes
xmlui.dri2xhtml.METS-1.0.item-coverage London
Language English
Sponsor INFAR/UNIFESP Confocal and Flow Cytometry Facility
Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
Grant number FAPESP: 2013/09068-7
FAPESP: 2015/16799-3
Date 2016
Published in Bmc Pharmacology & Toxicology. London, v. 17, p. -, 2016.
ISSN 2050-6511 (Sherpa/Romeo, impact factor)
Publisher Biomed Central Ltd
Extent -
Origin http://dx.doi.org/10.1186/s40360-016-0072-y
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000379528300001
URI https://repositorio.unifesp.br/handle/11600/57550

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