The P2X ₇ ATP Receptor in the Kidney: A Matter of Life or Death?

Abstract

P2X₇ is an intriguing membrane receptor for the extracellular nucleotide ATP, which functions as a ligand-gated ion channel; it can activate cell membrane permeabilization and also has a wide range of downstream signaling pathways, including mediation of inflammatory responses and modulation of cell turnover. Despite recent identification of P2X₇ receptor protein in the renal tract, the biological and potential pathological functions of this receptor and its signaling cascades in the kidney are not yet fully understood. P2X₇ receptor protein is expressed in normal kidney development, predominantly in the condensing mesenchyme, and later in the maturing and adult derivatives of the ureteric bud. Glomerular expression of the molecule is scarce in normal kidney, but is upregulated in chronic and inflammatory conditions, suggesting a role in the inflammatory response or in repair and remodeling in these settings. P2X₇ receptor expression in the adult collecting ducts of murine kidney, as well as the collecting duct cysts in autosomal recessive polycystic kidney disease, has been described and agonists of the receptor can modulate the development of renal cysts in an in vitro model of cyst formation derived from the cpk/cpk mouse. Further investigation of the function of the P2X₇ receptor in normal and abnormal kidneys might lead to novel therapeutic targets in a wide range of renal diseases.