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      Historadioautographic Localization, Pharmacology and Ontogeny of V 1a Vasopressin Binding Sites in the Rat Kidney

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          Abstract

          The localization and pharmacological characteristics of vasopressin (VP) binding sites of the V<sub>1a</sub> subtype in developing and adult rat kidney were investigated by radioautography on kidney sections incubated in the presence of a radioiodinated selective V<sub>1a</sub> antagonist. Their localization after in vivo systemic infusion of the radioligand was also investigated. V<sub>1a</sub> binding sites first appear at embryonic day 16 on vascular elements. In the adult, they were localized in the cortex (vascular and tubular structures, juxtaglomerular apparatus), the outer medulla outer stripe (vasa recta) and inner stripe (thin descending limbs of short looped nephrons) and the inner medulla (collecting ducts). Data obtained in vitro were confirmed by in vivo binding at postnatal day 30 (PN30). Whatever their localizations, the V<sub>1a</sub> binding sites exhibited full V<sub>1a</sub> pharmacological profile in postnatal stages rats and in adult rats: a high affinity (n M range) for VP and for the V<sub>1a</sub> agonist, a lower affinity (µ M range) for oxytocin and no affinity for the oxytocin agonist. The presence of V<sub>1a</sub> binding sites in these different structures raises the question of the putative roles of VP in modulating renal functions. A striking finding is the presence of V<sub>1a</sub> binding sites in the outer medullary thin descending limbs of short looped nephrons suggesting their colocalization with urea transporters.

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          Most cited references 5

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          Molecular cloning and expression of a rat V1a arginine vasopressin receptor.

          The neurohypophyseal hormone arginine vasopressin has diverse actions, including the inhibition of diuresis, contraction of smooth muscle, stimulation of liver glycogenolysis and modulation of adrenocorticotropic hormone release from the pituitary. Arginine vasopressin receptors are G protein-coupled and have been divided into at least three types; the V1a (vascular/hepatic) and V1b (anterior pituitary) receptors which act through phosphatidylinositol hydrolysis to mobilize intracellular Ca2+, and the V2 (kidney) receptor which is coupled to adenylate cyclase. We report here the cloning of a complementary DNA encoding the hepatic V1a arginine vasopressin receptor. The liver cDNA encodes a protein with seven putative transmembrane domains, which binds arginine vasopressin and related compounds with affinities similar to the native rat V1a receptor. The messenger RNA corresponding to the cDNA is distributed in rat tissues known to contain V1a receptors.
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            A radioiodinated linear vasopressin antagonist: A ligand with high affinity and specificity for V1areceptors

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              Autoradiographic localization of V1 vasopressin binding sites in rat brain and kidney.

              Monoiodination of the V1 vasopressin antagonist [Mca1,Sar7]AVP did not alter its high-affinity binding to liver plasma membranes. Monoradioiodinated [Mca1,125I-Tyr2,Sar7]AVP was therefore used to label V1-specific binding sites in the rat brain and kidney. The accumbens nucleus, the septal nucleus, the central amygdala, the bed nucleus of the stria terminalis, the stigmoid hypothalamic nucleus and the nucleus of the solitary tract exhibited specific labeling with both the radioiodinated V1 antagonist and tritiated AVP. Of the circumventricular structures only the choroid plexi and the area postrema showed V1-specific binding sites. The subfornical organ and hypothalamic loci of AVP synthesis such as the paraventricular nucleus, the supraoptic nucleus and the suprachiasmatic nucleus were not marked by the V1 antagonist while bearing [3H]AVP binding sites. As demonstrated by HPLC and binding to liver plasma membranes, the radiolabeled antagonist remained intact during tissue incubation. In addition to renal cortical and medullary [3H]AVP binding sites, medullary tubular and vascular structures could be labeled with the V1 antagonist, indicating the presence of both V1 and V2 AVP receptor subtypes in the rat kidney.
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                Author and article information

                Journal
                NEF
                Nephron
                10.1159/issn.1660-8151
                Nephron
                S. Karger AG
                1660-8151
                2235-3186
                1999
                September 1999
                31 August 1999
                : 83
                : 1
                : 74-84
                Affiliations
                UMR CNRS 7519, Université Louis-Pasteur, Strasbourg, France
                Article
                45476 Nephron 1999;83:74–84
                10.1159/000045476
                10461039
                © 1999 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: 4, Tables: 1, References: 52, Pages: 11
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/45476
                Categories
                Original Paper

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