Sustained Release of Prostaglandin E2 in Fibroblasts Expressing Ectopically Cyclooxygenase 2 Impairs P2Y-Dependent Ca2 -MobilizationReport as inadecuate

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Mediators of InflammationVolume 2014 2014, Article ID 832103, 9 pages

Research Article

Instituto de Investigaciones Biomédicas Alberto Sols, Centro Mixto CSIC-UAM, Arturo Duperier 4, 28029 Madrid, Spain

The Salk Institute, 10010 N Torrey Pines Road, La Jolla, CA 92037, USA

Departamento de Bioquímica y Biología Molecular IV, Facultad de Veterinaria e Instituto Universitario de Investigación en Neuroquímica, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos IdISSC, Universidad Complutense, Madrid, Spain

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Ciberehd, Spain

Received 30 May 2014; Accepted 1 August 2014; Published 18 August 2014

Academic Editor: Mireia Martín-Satué

Copyright © 2014 María Pimentel-Santillana et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The nucleotide uridine trisphosphate UTP released to the extracellular milieu acts as a signaling molecule via activation of specific pyrimidine receptors P2Y. P2Y receptors are G protein-coupled receptors expressed in many cell types. These receptors mediate several cell responses and they are involved in intracellular calcium mobilization. We investigated the role of the prostanoid PGE2 in P2Y signaling in mouse embryonic fibroblasts MEFs, since these cells are involved in different ontogenic and physiopathological processes, among them is tissue repair following proinflammatory activation. Interestingly, Ca

-mobilization induced by UTP-dependent P2Y activation was reduced by PGE2 when this prostanoid was produced by MEFs transfected with COX-2 or when PGE2 was added exogenously to the culture medium. This Ca

-mobilization was important for the activation of different metabolic pathways in fibroblasts. Moreover, inhibition of COX-2 with selective coxibs prevented UTP-dependent P2Y activation in these cells. The inhibition of P2Y responses by PGE2 involves the activation of PKCs and PKD, a response that can be suppressed after pharmacological inhibition of these protein kinases. In addition to this, PGE2 reduces the fibroblast migration induced by P2Y-agonists such as UTP. Taken together, these data demonstrate that PGE2 is involved in the regulation of P2Y signaling in these cells.

Author: María Pimentel-Santillana, Paqui G. Través, Raquel Pérez-Sen, Esmerilda G. Delicado, Paloma Martín-Sanz, María Teresa Mi



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