TRANSGENIC ANALYSIS OF CA SENSING RECEPTOR IN THE KIDNEY

细胞外钙敏感受体（CaSR）最有可能发挥作用， 在调节肾脏对钙的反应及其 其他电解质的处理，但其确切的功能和 在肾脏中的作用机制尚未阐明。 到 确定CaSR在肾脏中的作用， 在肾脏远端小管中过度表达CaSR将是 发展和过度表达的影响，随后增加 激活CaSR对整个动物生理和细胞生理的影响 考察 CaSR激活对肾小管上皮细胞远端小管的影响 肾对肾钙重吸收、单重浓缩 能力、顶端钾通道活性和环AMP生成 将测定对加压素的反应。 这项工作的潜在临床意义是深远的。 确定CaSR在肾脏中的作用肯定会阐明 CaSR突变导致的罕见遗传疾病，但它 还应该提高对初级过程的理解， 肾结石、骨质疏松、甲状旁腺疾病， 甚至原发性高血压。

The extracellular calcium-sensing receptor (CaSR) most likely plays a critical role in modulating the kidney's response to calcium and its processing of other electrolytes, but its exact function and mechanisms of action in the kidney have yet to be elucidated. To determine the role of CaSR in the kidney, a transgenic mouse model over expressing the CaSR in the distal tubules of the kidney will be developed and the effect of over expression and subsequent increased activation of CaSR on whole animal physiology and cellular physiology examined. The effect of activation of CaSR in the distal tubules of the kidney on renal calcium reabsorption, uniary concentrating ability, apical potassium channel activity, and cyclic-AMP generation in response to vasopressin will be determined. The potential clinical significance of this work is far-reaching. Determine the role of CaSR in the kidney will certainly shed light on the rare genetic disorders resulting from mutations in CaSR, but it should also improve understanding of primary processes in nephrolithiasis, osteoporosis, parathyroid disorders, and possibly even essential hypertension.