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      Calcium–Sensing Receptor: Regulation of Electrolyte Transport in the Thick Ascending Limb of Henle's Loop

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          Abstract

          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 Ca<sup>2+</sup> concentration. We observed that in the mouse CTAL cAMP formation, induced by 10<sup>–8</sup> mol/l AVP, was inhibited by more than 90% when the extracellular Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>e</sub>) was increased from 0.5 to 3 mmol/l. Measurements of transepithelial potential difference (PD<sub>te</sub>) 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 [Ca<sup>2+</sup>]<sub>e</sub> had no effect on basal and arginine vasopressin (AVP, 10<sup>–10</sup> mol/l)–stimulated transepithelial PD<sub>te</sub>, NaCl and Mg<sup>2+</sup> transport. However, Ca<sup>2+</sup> reabsorption was strongly inhibited by increased [Ca<sup>2+</sup>]<sub>e</sub>. Addition of AVP reversed this inhibitory effect of increased [Ca<sup>2+</sup>]<sub>e</sub>. Under hypotonic perfusion conditions (lumen 50 mmol/l NaCl; bath 150 mmol/l NaCl), a high [Ca<sup>2+</sup>]<sub>e</sub> induced a 50% decrease in Mg<sup>2+</sup> reabsorption which was restored by AVP. Under these conditions, the effects on Ca<sup>2+</sup> 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 Ca<sup>2+</sup> and Mg<sup>2+</sup> reabsorption.

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          Most cited references 6

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          Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling.

           Tony Hunter (1995)
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            Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid.

            Maintenance of a stable internal environment within complex organisms requires specialized cells that sense changes in the extracellular concentration of specific ions (such as Ca2+). Although the molecular nature of such ion sensors is unknown, parathyroid cells possess a cell surface Ca(2+)-sensing mechanism that also recognizes trivalent and polyvalent cations (such as neomycin) and couples by changes in phosphoinositide turnover and cytosolic Ca2+ to regulation of parathyroid hormone secretion. The latter restores normocalcaemia by acting on kidney and bone. We now report the cloning of complementary DNA encoding an extracellular Ca(2+)-sensing receptor from bovine parathyroid with pharmacological and functional properties nearly identical to those of the native receptor. The novel approximately 120K receptor shares limited similarity with the metabotropic glutamate receptors and features a large extracellular domain, containing clusters of acidic amino-acid residues possibly involved in calcium binding, coupled to a seven-membrane-spanning domain like those in the G-protein-coupled receptor superfamily.
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              Co-expression of a Ca2+-inhibitable Adenylyl Cyclase and of a Ca2+-sensing Receptor in the Cortical Thick Ascending Limb Cell of the Rat Kidney: INHIBITION OF HORMONE-DEPENDENT cAMP ACCUMULATION BY EXTRACELLULAR Ca2+

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                Author and article information

                Journal
                KBR
                Kidney Blood Press Res
                10.1159/issn.1420-4096
                Kidney and Blood Pressure Research
                S. Karger AG
                1420-4096
                1423-0143
                1998
                1998
                06 February 1999
                : 21
                : 6
                : 401-412
                Affiliations
                aURA CNRS 1859, Département de Biologie Cellulaire et Moléculaire, CEA Saclay, Gif–sur–Yvette, France; bCattedra di Nefrologia, Dipartimento di Pediatria, Seconda Universitá degli Studi di Napoli, Italia; cINSERM, Unité 367, Paris, France
                Article
                25892 Kidney Blood Press Res 1998;21:401–412
                10.1159/000025892
                9933824
                © 1998 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 5, Tables: 3, References: 47, Pages: 12
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/25892
                Categories
                Original Paper

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