The Pattern of Distribution of Selected ATP-Sensitive P2 Receptor Subtypes in Normal Rat Kidney: An Immunohistological Study

Abstract

Using immunohistological techniques and available polyclonal antibodies, we have identified several ATP-sensitive P2 receptor subtypes in specific structures of the normal rat kidney. Of the P2 receptor subtypes examined, P2X₁, P2X₂ and P2Y₁ receptors were found in the smooth muscle layer of intrarenal vessels. The P2Y₁ receptor was also found on glomerular mesangial cells, the brush border membrane of the proximal straight tubule and on peritubular fibroblasts. In the cortex, P2Y₄ receptors were found on the tubule epithelium of the proximal convoluted tubule, and P2Y₂ receptors on glomerular epithelial cells (podocytes). P2X₄ and P2X₆ receptors were present throughout the renal tubule epithelium from the proximal tubule to the collecting duct. P2X₅ receptors were expressed on medullary collecting duct cells and the apical membrane of the S3 segment of the proximal tubule. Possible functions of these receptor subtypes in normal rat kidney are discussed.

Purinergic signalling in the kidney in health and disease

“…Cultured human podocytes produce superoxide in response to extracellular ATP [115]. Increase in [Ca 2+ ] i by purines and pyrimidines is mediated mainly by P2Y 2 and P2Y 6 receptors, but P2Y 1 , P2Y 11 and P2X7 receptors are also expressed by podocytes [40,87,118,375]. ATP acting via P2 receptors stimulated AMP-activated protein kinase and suppressed superoxide generation in cultured mouse podocytes [287].…”

“…Kidney blood vessels P2X1 receptors have been identified in the vascular smooth muscle of the rat renal, arcuate and interlobular arteries and in the afferent arteriole: P2X1 is not expressed in the efferent arteriole [51,375]. A P2X1-like receptor has been confirmed functionally in the afferent arteriole [149].…”

“…A P2X1-like receptor has been confirmed functionally in the afferent arteriole [149]. In the smooth muscle of the larger renal arteries, P2X2 receptor subunits have been immunolocalised [146,375], and at a molecular level, P2X4 receptor subunits are found, at least in arcuate and interlobular arteries [127]. At a protein level, however, P2X4 expression is limited to the vascular endothelium [242].…”

“…P2X7 receptors are also expressed in the healthy kidney: expression in the vascular smooth muscle and outeradventitium is very low [218], whereas functionally significant expression is observed in the endothelium [242]. Of the P2Y receptors, P2Y 1 is expressed in the endothelium of the large arteries and both afferent and efferent arterioles [375]. ATP released from renal tubular epithelial cells acts on pericytes to regulate the diameter of vasa recta capillaries that are in close proximity to renal tubules and are key to Fig.…”

“…The pattern and distribution of P1 [345,390] and P2 receptors [14,49,375] along the rat renal tubule have been reported (see Fig. 3), and the major transporters for sodium and water are illustrated in Fig.…”