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      Analysis of Angiotensin II Receptor Subtypes in Individual Rat Brain Nuclei

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          Abstract

          Previous studies have used new angiotensin II (AII) receptor subtype selective compounds to localize AII receptor subtypes within discrete rat brain nuclei. The purpose of this autoradiographic study was to extend these preliminary findings and provide a comprehensive analysis of AII binding sites in 22 rat brain nuclei and the anterior pituitary, to include estimates of the binding affinity for <sup>125</sup>I sar<sup>1</sup> ile<sup>8</sup> AII (<sup>125</sup>I SIAII) at each nucleus, and determine the fractional distribution of each subtype at each nucleus. Estimates of K<sub>D</sub> in separate experiments revealed that AT<sub>1</sub> nuclei had a consistently higher affinity for <sup>125</sup>I SIAII than AT<sub>2</sub> nuclei (0.66 vs. 2.55 n M). Displacement of subsaturating concentrations of <sup>125</sup>I SIAII by 10<sup>–8</sup>–10<sup>–4</sup> M DuP753 (selective for the AT<sub>1</sub> subtype) or PD123177 (selective for the AT<sub>2</sub> subtype) indicated that approximately half of the brain regions surveyed contained predominantly AT<sub>1</sub> sites and half contained predominantly AT<sub>2</sub> sites. Binding was partially displaced by both compounds in several regions and two site analyses were performed to estimate the distribution of subtypes within each nucleus. The data were then corrected for differential occupancy by <sup>125</sup>I SIAII. Brain nuclei associated with cardiovascular or dipsogenic actions of AII, e.g., subfornical organ, organum vasculosum of the lamina terminalis, median preoptic nucleus, nucleus of the solitary tract and area postrema, contained pure, or almost pure, populations of AT<sub>1</sub> receptors. The functions of AII in brain regions containing predominantly AT<sub>2</sub> binding sites, e.g., thalamus, colliculi, inferior olive and locus ceruleus, remain undefined. Thus, AII binding sites in the rat brain have been differentiated into two subtypes with similar characteristics to those reported in peripheral tissues. However, the unexpected finding that they can be differentiated on the basis of their affinity for <sup>125</sup>I SIAII raises questions concerning their coidentity with peripheral receptor subtypes.

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          Author and article information

          Journal
          NEN
          Neuroendocrinology
          10.1159/issn.0028-3835
          Neuroendocrinology
          S. Karger AG
          0028-3835
          1423-0194
          1992
          1992
          07 April 2008
          : 55
          : 5
          : 563-573
          Affiliations
          aDepartment of Physiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tenn; bDepartment of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, Wash., USA
          Article
          126177 Neuroendocrinology 1992;55:563–573
          10.1159/000126177
          1584339
          © 1992 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
          Pages: 11
          Categories
          Original Paper

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