Calcium-sensing receptor: Regulation of electrolyte transport in the thick ascending limb of Henle's loop

Calcium-sensing receptor: Regulation of electrolyte transport in the thick ascending limb of Henle's loop
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DOI:
10.1159/000025892
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发表时间:
1998-01-01
影响因子:
2.8
通讯作者:
Di Stefano, A
Di Stefano, A
中科院分区:
医学4区
文献类型:
--
作者:
Desfleurs, E;Wittner, M;Di Stefano, A

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钙敏感受体(CaR)在大鼠和小鼠的汉勒氏袢(CTAL)的皮质厚升支中具有功能性。这种G蛋白偶联受体激活磷脂酶C并增加细胞内Ca 2+浓度。当细胞外Ca ~(2+)浓度([Ca ~(2+)](e))从0.5增加到3 mmol/l时,10(-8)mol/l AVP诱导的小鼠CTAL cAMP生成被抑制90%以上。测量大鼠和小鼠CTAL和髓质升支粗段(mTAL)中的跨上皮电位差(PDte)以及小鼠CTAL中的跨上皮离子净通量(等渗灌注条件:150 mmol/l NaCl)表明,[Ca 2 +](e)的增加对基础和精氨酸加压素没有影响(AVP,10(-10)mol/l)刺激PDte、NaCl和Mg ~(2+)的跨上皮转运。然而,[Ca ~(2+)](e)的增加强烈抑制Ca ~(2+)的重吸收。AVP可逆转[Ca ~(2+)]_i增加的抑制作用。在低渗灌流条件下(腔50 mmol/l NaCl;浴150 mmol/l NaCl),高[Ca ~(2+)](e)引起Mg ~(2+)重吸收减少50%,AVP可使Mg ~(2+)重吸收恢复。在这些条件下,仍然观察到上述对Ca 2+转运的影响。总之,激活小鼠TAL中的CaR对基础和AVP刺激的跨上皮NaCl重吸收没有影响,尽管其对cAMP合成有很大的抑制作用。而CaR在调节跨上皮Ca ~(2+)和Mg ~(2+)重吸收中起一定作用。
A calcium-sensing receptor (CaR) has functionally been described in the cortical thick ascending limb of Henle's loop (CTAL) of rat and mouse. This G protein-coupled receptor activates phospholipase C and increases the intracellular Ca2+ concentration. We observed that in the mouse CTAL cAMP formation, induced by 10(-8) mol/l AVP, was inhibited by more than 90% when the extracellular Ca2+ concentration ([Ca2+](e)) was increased from 0.5 to 3 mmol/l. Measurements of transepithelial potential difference (PDte) in rat and mouse CTAL and medullary thick ascending limb (mTAL) segments and of transepithelial ion net fluxes in the mouse CTAL (isotonic perfusion conditions: 150 mmol/l NaCl in the lumen and bath) showed that an increase in the [Ca2+](e) had no effect on basal and arginine vasopressin (AVP, 10(-10) mol/l)stimulated transepithelial PDte, NaCl and Mg2+ transport. However, Ca2+ reabsorption was strongly inhibited by increased [Ca2+](e). Addition of AVP reversed this inhibitory effect of increased [Ca2+],. Under hypotonic perfusion conditions (lumen 50 mmol/l NaCl; bath 150 mmol/l NaCl), a high (Ca2+](e) induced a 50% decrease in Mg2+ reabsorption which was restored by AVP. Under these conditions, the effects on Ca2+ transport described above were still observed. In conclusion, activation of the CaR in the mouse TAL has no effect on basal and AVP-stimulated transepithelial NaCl reabsorption despite its large inhibitory effect on cAMP synthesis. The CaR, however, could play a role in the regulation of transepithelial Ca2+ and Mg2+ reabsorption.