P2X and P2Y receptor signaling in red blood cells.

Ronald Sluyter

doi:10.3389/fmolb.2015.00060

Abstract

Purinergic signaling involves the activation of cell surface P1 and P2 receptors by extracellular nucleosides and nucleotides such as adenosine and adenosine triphosphate (ATP), respectively. P2 receptors comprise P2X and P2Y receptors, and have well-established roles in leukocyte and platelet biology. Emerging evidence indicates important roles for these receptors in red blood cells. P2 receptor activation stimulates a number of signaling pathways in progenitor red blood cells resulting in microparticle release, reactive oxygen species formation, and apoptosis. Likewise, activation of P2 receptors in mature red blood cells stimulates signaling pathways mediating volume regulation, eicosanoid release, phosphatidylserine exposure, hemolysis, impaired ATP release, and susceptibility or resistance to infection. This review summarizes the distribution of P2 receptors in red blood cells, and outlines the functions of P2 receptor signaling in these cells and its implications in red blood cell biology.

Highlights

It is well-established that extracellular adenosine triphosphate (ATP) and other nucleotides function through cell surface purinergic receptors to mediate numerous signaling events in all cell types (Burnstock and Knight, 2004)
Unlike P2X receptors, some P2Y receptor subtypes are preferentially activated by nucleotides other than ATP, such as P2Y2 and P2Y13, which are preferentially activated by uridine triphosphate (UTP) and adenosine diphosphate (ADP), respectively
This review aims to provide an overview of the distribution of P2 receptors on red blood cells (RBCs) progenitors and mature RBCs, and to outline the functions of P2 receptor signaling in these cell types

Summary

Introduction

It is well-established that extracellular adenosine triphosphate (ATP) and other nucleotides function through cell surface purinergic receptors to mediate numerous signaling events in all cell types (Burnstock and Knight, 2004). It was demonstrated that P2X7 activation mediates ATP-induced rapid dye uptake and apoptosis in MEL cells (Constantinescu et al, 2010). P2X7 activation in MEL cells induces rapid phosphatidylserine (PS) exposure, microparticle release, apoptosis (Constantinescu et al, 2010) and reactive oxygen species formation (Wang and Sluyter, 2013).

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