Vezzoli Giuseppe, Soldati Laura, Gambaro Giovanni
Nephrology Division, Columbus-Gemelli Hospital, Catholic University, Rome, Italy.
Curr Pharm Biotechnol. 2009 Apr;10(3):302-10. doi: 10.2174/138920109787847475.
Calcium-sensing receptor (CaSR), a member of family C of the G protein-coupled receptors, is expressed most abundantly in the parathyroid glands and kidney. It plays key role in these two organs because it senses changes in extracellular calcium and regulates PTH secretion and calcium reabsorption to suit the extracellular calcium concentration. In kidney, CaSR is expressed in all nephron segments. It has an inhibitory effect on the reabsorption of calcium, potassium, sodium and water, depending on the particular function of the different tubular tracts. Among its inhibitory effects, CaSR modulates the signaling pathways used by the tubulocytes to activate electrolyte or water reabsorption. The only site where there is no such inhibitory effect is in the proximal tubule, where CaSR enhances phosphate reabsorption to counteract the effect of PTH. CaSR mutations and polymorphisms cause disorders characterized by alterations in renal excretion and serum calcium concentrations. They also can cause sodium and potassium excretion disorders. CaSR also mediates the acute adverse renal effects of hypercalcemia, which include a reduced sodium, potassium and water reabsorption. From a teleological perspective, CaSR seems to protect human tissues against calcium excess in extracellular fluids.
钙敏感受体（CaSR）是G蛋白偶联受体C家族的成员，在甲状旁腺和肾脏中表达最为丰富。它在这两个器官中发挥关键作用，因为它能感知细胞外钙的变化，并调节甲状旁腺激素（PTH）分泌和钙重吸收，以适应细胞外钙浓度。在肾脏中，CaSR在所有肾单位节段均有表达。根据不同肾小管节段的特定功能，它对钙、钾、钠和水的重吸收具有抑制作用。在其抑制作用中，CaSR调节肾小管细胞用于激活电解质或水重吸收的信号通路。唯一没有这种抑制作用的部位是近端小管，在近端小管中CaSR增强磷酸盐重吸收以抵消PTH的作用。CaSR突变和多态性会导致以肾排泄和血清钙浓度改变为特征的疾病。它们还可导致钠和钾排泄紊乱。CaSR还介导高钙血症的急性不良肾脏效应，包括钠、钾和水重吸收减少。从目的论的角度来看，CaSR似乎能保护人体组织免受细胞外液中钙过量的影响。
