Bailey M A, Imbert-Teboul M, Turner C, Marsy S, Srai K, Burnstock G, Unwin R J
Centre for Nephrology, Autonomic Neuroscience Institutes, University College London, London, England, United Kingdom.
Kidney Int. 2000 Nov;58(5):1893-901. doi: 10.1111/j.1523-1755.2000.00361.x.
Several groups have identified P2Y receptors in the basolateral membrane of the rat nephron. These studies have not covered all segments of the nephron and have relied solely on the relative potency of receptor agonists for classification.
We measured purine and pyrimidine-induced changes in intracellular free calcium concentration (Ca(2+)) in anatomically defined segments of the rat nephron. To complement these functional studies, we have used reverse transcription-polymerase chain reaction methodology to identify specific P2Y receptor transcripts in these segments.
Adenosine 5'-triphosphate (ATP) mobilized Ca(2+) in all nephron segments, except for the thick ascending limb of Henle, which was poorly responsive. Adenosine (100 micromol/L) was without effect, confirming that the effect of ATP was mediated by P2 receptors. In the proximal convoluted tubule (PCT) and outer medullary collecting duct (OMCD), there was evidence for 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 presence 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 segments. In the PCT and OMCD and thin ascending limb of Henle, we found expression of P2Y(1), P2Y(2), and P2Y(4) receptors. In the descending limb of Henle, P2Y(1) and P2Y(2) mRNA was found, but P2Y(4) was not expressed.
These data suggest that extracellular ATP can influence tubular cell function in all segments of the rat nephron, through P2Y receptors via multiple (and coexpressed) P2Y receptor subtypes.
多个研究小组已在大鼠肾单位的基底外侧膜中鉴定出P2Y受体。这些研究并未涵盖肾单位的所有节段，且仅依靠受体激动剂的相对效价进行分类。
我们测量了嘌呤和嘧啶诱导的大鼠肾单位解剖学定义节段内细胞内游离钙浓度（[Ca(2+)]i）的变化。为补充这些功能研究，我们使用逆转录-聚合酶链反应方法来鉴定这些节段中特定的P2Y受体转录本。
三磷酸腺苷（ATP）可使除亨氏袢粗升支外的所有肾单位节段中的[Ca(2+)]i升高，而亨氏袢粗升支对此反应较弱。腺苷（100 μmol/L）无作用，证实ATP的作用是由P2受体介导的。在近端曲管（PCT）和外髓集合管（OMCD）中，有证据表明存在两种具有P2Y(1)以及类似P2Y(2)或P2Y(4)受体特征的受体亚型。细段中的一个新发现是存在一种兼具P2Y(2)和P2Y(4)受体亚型特性的受体。为辅助分类，我们在大鼠肾单位节段中鉴定出P2Y受体mRNA。在PCT、OMCD和亨氏袢细升支中，我们发现了P2Y(1)、P2Y(2)和P2Y(4)受体的表达。在亨氏袢降支中，发现了P2Y(1)和P2Y(2) mRNA，但未表达P2Y(4)。
这些数据表明，细胞外ATP可通过多种（且共表达的）P2Y受体亚型，经由P2Y受体影响大鼠肾单位所有节段的肾小管细胞功能。
