The effects of streptozocin‐induced type I diabetes on P2 receptors profile in the podocytes of the Dahl SS rat glomeruli (689.6)

Abstract

Calcium flux in the podocytes is critical for their physiological function; excessive calcium in these cells can result in glomeruli damage, proteinuria and reduced GFR. P2 receptors are located throughout the kidney, and upon binding of ATP they activate calcium influx that triggers a plethora of intracellular processes. Our previous data have demonstrated that the major P2 receptor in the Sprague Dawley rat podocytes is P2Y1. Diabetic conditions have been shown to cause glomeruli injury and alter purinergic receptors profile in the kidney. The goal of the current study was to identify the P2 receptors responsible for calcium flux in the podocytes of the rats with type I diabetes. Type I diabetes was induced in the Dahl salt‐sensitive (SS) rats by an injection of streptozocin followed by an insulin implant, which results in the development of hyperfiltration, progressive proteinuria and renal damage typical for diabetic nephropathy. After 6 weeks of treatment, the glomeruli of the rats were isolated by differential sieving, loaded with Fluo‐4/FuraRed calcium dyes and analyzed with real‐time ratiometric fluorescent measurements. Pharmacological agonists and antagonists of the P2X and P2Y receptors were utilized to determine P2 receptors profile under diabetic conditions. This study will define the P2 receptors involved in the pathogenesis of the glomerular injury in diabetes, which could lead to a targeted treatment for renal complications associated with this disease.