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      Cell-Specific Expression of the IP 3 Receptor Gene Family in the Kidney

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          Abstract

          Background/Aim: The localization of inositol trisphosphate (IP<sub>3</sub>) receptor isoforms, types 1–3, in the kidney and their role in the regulation of the intracellular calcium concentration – [Ca<sup>2+</sup>]<sub>i</sub> – are discussed. Methods: Immunohistological studies with isoform-specific antibodies were performed to reveal the localization of IP<sub>3</sub> receptor isoforms. To examine the role of IP<sub>3</sub> receptor type 1 in the glomeruli, the responses of [Ca<sup>2+</sup>]<sub>i</sub> to hormonal stimuli were examined in IP<sub>3</sub> receptor type 1 knockout mice. Results: In the immunohistological study, type 1 receptor was present in arteries, afferent arterioles, and mesangial cells. Double staining with antibodies against aquaporin 2 and IP<sub>3</sub> type 2 receptor revealed that type 2 receptor was localized mainly in the intercalated cells. The type 3 receptor showed characteristic intracellular localization in the collecting duct cells of the cortex to the outer medulla. Immunostaining of type 3 receptor was most intense in the cytoplasm on the basolateral membrane side and was not seen on the apical side. The responses of [Ca<sup>2+</sup>]<sub>i</sub> to angiotensin II and endothelin in the glomeruli were markedly attenuated in IP<sub>3</sub> receptor type 1 knockout mice. Conclusions: The three isoforms of the IP<sub>3</sub> receptor showed distinctive localization in the kidney, and the type 1 receptor plays a major role in the regulation of [Ca<sup>2+</sup>]<sub>i</sub> in the glomeruli. The physiological significance of the cell-specific localization, however, remains to be determined.

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          Most cited references 5

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          Ataxia and epileptic seizures in mice lacking type 1 inositol 1,4,5-trisphosphate receptor.

           O Minowa,  H Takano,  T Noda (1996)
          The inositol 1,4,5-trisphosphate (InsP3) receptor acts as an InsP3-gated Ca2+ release channel in a variety of cell types. Type 1 InsP3 receptor (IP3R1) is the major neuronal member of the IP3R family in the central nervous system, predominantly enriched in cerebellar Purkinje cells but also concentrated in neurons in the hippocampal CA1 region, caudate-putamen, and cerebral cortex. Here we report that most IP3R1-deficient mice generated by gene targeting die in utero, and born animals have severe ataxia and tonic or tonic-clonic seizures and die by the weaning period. An electroencephalogram showed that they suffer from epilepsy, indicating that IP3R1 is essential for proper brain function. However, observation by light microscope of the haematoxylin-eosin staining of the brain and peripheral tissues of IP3R1-deficient mice showed no abnormality, and the unique electrophysiological properties of the cerebellar Purkinje cells of IP3R1-deficient mice were not severely impaired.
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            Primary structure and functional expression of the inositol 1,4,5-trisphosphate-binding protein P400.

            Cloning and expression of functional P400 protein from cerebellar Purkinje neurons shows that this protein is a receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium.
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              Heterotetrameric complex formation of inositol 1,4,5-trisphosphate receptor subunits.

              The inositol 1,4,5-trisphosphate receptor (IP3R) exists as a tetrameric complex to form a functional inositol 1,4,5-trisphosphate-gated Ca2+ channel. Molecular cloning studies have shown that there are at least three types of IP3R subunits, designated type 1, type 2, and type 3. The levels of expression of IP3R subunits in various cell lines were investigated by Western blot analysis using type-specific antibodies against 15 C-terminal amino acids of each IP3R subunit. We found that all the three types of IP3R subunits were expressed in each cell line examined, but their levels of expression varied. To determine whether IP3Rs form heterotetramers, we employed immunoprecipitation experiments using Chinese hamster ovary cells (CHO-K1 cells), in which all three types are abundantly expressed. Each type-specific antibody immunoprecipitated not only the respective cognate type but also the other two types. This result suggests that distinct types of IP3R subunits assemble to form heterotetramers in CHO-K1 cells. We also detected heterotetramers in rat liver, in which IP3R type 1 and type 2 are expressed abundantly. Previous studies have shown some functional differences among IP3R types, suggesting the possibility that various compositions of subunits show distinct channel properties. The diversity of IP3R channels may be further increased by the co-assembly of different IP3R subunits to form homo- or heterotetramers.
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                Author and article information

                Journal
                EXN
                Nephron Exp Nephrol
                10.1159/issn.1660-2129
                Cardiorenal Medicine
                S. Karger AG
                1660-2129
                2000
                October 2000
                31 July 2000
                : 8
                : 4-5
                : 215-218
                Affiliations
                Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
                Article
                20671 Exp Nephrol 2000;8:215–218
                10.1159/000020671
                10940719
                © 2000 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: 1, References: 15, Pages: 4
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/20671
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