Axial distribution and characterization of basolateral P2Y receptors alongthe rat renal tubule

Background. Several groups have identified P2Y receptors in the basolateral membrane of the rat nephron. These studies have not covered all segments o f the nephron and have relied solely on the relative potency of receptor ag onists for classification. Methods. We measured purine and pyrimidine-induced changes in intracellular free calcium concentration ([Ca2+](i)) in anatomically defined segments of the rat nephron. To complement these functional studies, we have used reve rse transcription-polymerase chain reaction methodology to identify specifi c P2Y receptor transcripts in these segments. Results. Adenosine 5'-triphosphate (ATP) mobilized [Ca2+](i) in all nephron segments, except for the thick ascending limb of Henle, which was poorly r esponsive. Adenosine (100 mu mol/L) was without effect, confirming that the effect of ATP was mediated by P2 receptors. In the proximal convoluted tub ule (PCT) and outer medullary collecting duct (OMCD), there was evidence fo r two receptor subtypes with characteristics of P2Y(1-) and either P2Y(2)- or P2Y(4)-like receptors. A novel finding in the thin limbs was the presenc e of a receptor with properties of both P2Y(2) and P2Y(4) receptor subtypes . To aid classification, we identified P2Y receptor mRNA in rat nephron seg ments. In the PCT and OMCD and thin ascending limb of Henle, we found expre ssion of P2Y(1), P2Y(2), and P2Y(4), receptors. In the descending limb of H enle, P2Y(1) and P2Y(2) mRNA was found, but P2Y(4) was not expressed. Conclusion. These data suggest that extracellular ATP can influence tubular cell function in all segments of the rat nephron, through P2Y receptors vi a multiple (and coexpressed) P2Y receptor subtypes.