Pharmacological characterization of the P2 receptors profile in the podocytes of the Sprague Dawley rat glomeruli

Abstract

Renal P2 purinoreceptors are widely distributed throughout glomeruli, vasculature and tubular segments of the kidney. Extracellular ATP can mobilize calcium in the podocytes by activating these receptors and therefore contribute to glomeruli functions. The goal of this study was to identify specific P2 receptor subtypes in the podocytes of the rat glomeruli. The glomeruli of the Sprague Dawley rats were isolated by differential sieving, loaded with Fluo‐4/Fura Red calcium dyes and analysed with real‐time ratiometric fluorescent measurements under the confocal scope. Various specific chemical agonists and antagonists of the P2Y and P2X receptor subfamilies were utilized to determine responsible receptors under zero or 2 mM Ca2+ extracellular conditions. In contrast to previously published data, we have identified P2Y1 receptor as the main functional P2 receptor in the podocytes. Furthermore, we have assessed the contraction rates of the glomeruli in response to ATP and other P2Y1 receptors agonists therefore having shown the role of the P2 receptors, particularly, P2Y1, in the regulation of the glomerular volume dynamics. As a result of this study we identified P2Y1 as the main purinergic receptor localized in the podocytes, which might be involved in the pathogenesis of glomerular injury and in contraction and relaxation of glomeruli. Supported by the NIH (HL108880).