Riccardi D, Lee W S, Lee K, Segre G V, Brown E M, Hebert S C
Laboratory of Molecular Physiology and Biophysics, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Am J Physiol. 1996 Oct;271(4 Pt 2):F951-6. doi: 10.1152/ajprenal.1996.271.4.F951.
Using a strategy based on homology to the bovine parathyroid Ca(2+)-sensing receptor previously identified by us (5), we have recently isolated an extracellular, G protein-coupled Ca2+/ polyvalent cation-sensing receptor, RaKCaR (22), from rat kidney. The localization and physiological role(s) of this receptor in the kidney are not well understood. In the present study, we assessed the distribution of mRNAs for RaKCaR and the parathyroid hormone/parathyroid hormone-related protein (PTH/PTHrP) receptor along the rat nephron by in situ hybridization and reverse transcriptase-polymerase chain reaction of microdissected nephron segments. Our results show that transcripts for both receptors coexpress at glomeruli, proximal convoluted tubule, proximal straight tubule, cortical thick ascending limb, distal convoluted tubule, and cortical collecting duct. In addition, RaKCaR (but not PTH/PTHrP receptor) transcripts were found in the medullary thick ascending limb and outer medullary and inner medullary collecting ducts. These findings raise the possibility of roles for RaKCaR not only in the regulation of divalent mineral reabsorption but also in water reabsorption and urinary concentration. Taken together, our results provide new insights in understanding the effects of hypercalcemia on hormone-stimulated salt and water transport.
利用一种基于与我们之前鉴定的牛甲状旁腺钙敏感受体(5)同源性的策略,我们最近从大鼠肾脏中分离出一种细胞外G蛋白偶联的钙/多价阳离子敏感受体RaKCaR(22)。该受体在肾脏中的定位和生理作用尚不清楚。在本研究中,我们通过原位杂交以及对显微切割的肾单位节段进行逆转录聚合酶链反应,评估了RaKCaR和甲状旁腺激素/甲状旁腺激素相关蛋白(PTH/PTHrP)受体的mRNA在大鼠肾单位中的分布。我们的结果表明,两种受体的转录本在肾小球、近端曲管、近端直管、皮质厚升支、远端曲管和皮质集合管中共同表达。此外,在髓质厚升支以及外髓和内髓集合管中发现了RaKCaR(而非PTH/PTHrP受体)的转录本。这些发现提示,RaKCaR不仅在二价矿物质重吸收的调节中发挥作用,而且在水重吸收和尿液浓缩中也可能发挥作用。综上所述,我们的结果为理解高钙血症对激素刺激的盐和水转运的影响提供了新的见解。