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

A calcium-sensing receptor (CaR) has functionally been described in the cor tical thick ascending limb of Henle's loop (CTAL) of rat and mouse. This G protein-coupled receptor activates phospholipase C and increases the intrac ellular Ca2+ concentration. We observed that in the mouse CTAL cAMP formati on, induced by 10(-8) mol/l AVP, was inhibited by more than 90% when the ex tracellular 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 transe pithelial 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)st imulated transepithelial PDte, NaCl and Mg2+ transport. However, Ca2+ reabs orption was strongly inhibited by increased [Ca2+](e). Addition of AVP reve rsed 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. Unde r these conditions, the effects on Ca2+ transport described above were stil l observed. In conclusion, activation of the CaR in the mouse TAL has no ef fect 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.