P2X receptors and kidney function

Accumulating evidence indicates that the ATP/P2 receptor system, acting in an autocrine or paracrine manner, can affect a wide range of renal functions. P2X receptor subunits have been identified in most renal vessels and in every nephron segment; ATP is released from renal epithelial cells; and enzymes responsible for ATP degradation are expressed in the vasculature and tubules. Stimulation of P2X₁ receptors in the afferent arterioles by ATP released from renal nerve terminals or from adjacent macula densa cells induces vasoconstriction and contributes to the regulation of renal haemodynamics. In the tubule, there is evidence for a variety of P2X-mediated effects: inhibition of proximal tubular reabsorption; inhibition of Na⁺K⁺2Cl^- cotransporter activity (via increased nitric oxide synthesis) in the thick ascending limb of the loop of Henle; inhibition of magnesium reabsorption in the distal tubule; and modulation of sodium and water reabsorption in the collecting duct. Finally, P2X receptors, particularly P2X₇ subunits, appear to play an important role in renal pathology, specifically for cyst formation in polycystic kidney disease and in renal inflammation.