Purinergic P2 receptors: Involvement and therapeutic implications in diabetes-related glomerular injury.

The purinergic activation of P2 receptors initiates a powerful and rapid signaling cascade that contributes to the regulation of an array of physiological and pathophysiological processes in many organs, including the kidney. P2 receptors are broadly distributed in both epithelial and vascular renal cells. Disturbances of purinergic signaling can lead to impairments in renal function. A growing body of evidence indicates changes in P2 receptor expression and nucleotide metabolism in chronic renal injury and inflammatory diseases. Increasing attention has focused on purinergic P2X7 receptors, which are not normally expressed in healthy kidney tissue but are highly expressed at sites of tissue damage and inflammation. Under hyperglycemic conditions, several mechanisms that are linked to purinergic signaling and involve nucleotide release and degradation are disrupted, resulting in the accumulation of adenosine 5'-triphosphate in the bloodstream in diabetes. Dysfunction of the purinergic system might be associated with serious vascular complications in diabetes, including diabetic nephropathy. This review summarizes our current knowledge of the role of P2 receptors in diabetes-related glomerular injury and its implications for new therapeutics for diabetic nephropathy.