Vascular and inflammatory actions of P2X receptors in renal injury.

Abstract

P2 purinergic receptors are activated by extracellular ATP and subserve a plethora of roles in the body, including metabolism, inflammation and neuronal signalling. This review focuses on renal purinergic receptors and how different roles that they play may contribute to renal dysfunction and the progression of chronic kidney disease. Numerous studies have linked P2 receptors, particularly the P2X4R and P2X7R subtypes, to kidney injury and damage. However, the mechanisms underlying this association are not fully defined. Several studies show that activation of P2X4R and particularly P2X7R can have a pro-inflammatory effect, causing or exacerbating damage to renal tissue. However, clinical trials aiming to utilise P2X7R antagonists to treat inflammatory disease have been unsuccessful, and it is possible that other mechanisms besides inflammation tie P2X7R activation to disease progression. In this context, purinergic signalling is also involved in the control of vascular tone and our recent studies suggest that activation of P2X4R/P2X7R causes renal vascular dysfunction and contributes to chronic kidney disease. This brief review aims to summarise the complementary inflammatory and vascular roles of P2X receptors in the kidney, with emphasis on the subtypes P2X4R and P27XR, and how each contributes to and presents therapeutic targets in the progression of chronic kidney disease.