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      Regulation of Dopamine-Induced Natriuresisby the Dopamine-Metabolizing Enzyme Catechol-O-Methyltransferase

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          Abstract

          Dopamine (DA) is an intrarenal natriuretic hormone involved in sodium homeostasis. A study was performed to elucidate two possible regulatory pathways of DA-induced natriuresis, i.e., metabolism and precursor delivery. This was done by use of an intraperitoneal injection of a catechol-O-methyltransferase (COMT) inhibitor, entacapone, or intravenous infusion of the DA precursor, L-dopa. Entacapone (30 mg/kg i.p.) induced a more than fivefold increase in renal sodium excrection which occurred without changes in renal haemodynamics. The natriuretic response was highly dependent on DA D<sub>1</sub>-like receptor activation, since the selective D<sub>1</sub>-like receptor antagonist SCH23390 attenuated the natriuretic response by 61%, while the selective D<sub>2</sub>-like receptor antagonist sulpiride was ineffective. The urinary excretion of DA did not increase. Infusion of L-dopa (60 μg/h/kg) only induced a twofold increase in sodium excretion, but the urinary excretion of DA increased more than 17-fold. The L-dopa-induced natriuretic response occurred without increments in glomerular filtration rate and could be blocked with the D<sub>1</sub>-like receptor antagonist SCH23390. It is concluded that the DA-metabolizing enzyme COMT is involved in the regulation of the natriuretic effect of intrarenal DA. It may be speculated that intrarenal DA activity is not primarily determined on the basis of delivered precursor, but on that of the level of DA metabolism.

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          Most cited references 3

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          Dopamine-induced recruitment of dopamine D1 receptors to the plasma membrane.

          The recruitment of G protein-coupled receptors from the cytoplasm to the plasma membrane generally is believed to be a constitutive process. We show here by the use of both confocal microscopy and subcellular fractionation that, for at least one such receptor, this recruitment is regulated and not constitutive. Cells from a proximal tubular-like cell line, LLCPK1 cells, were incubated with either a D1 agonist, a dopamine precursor, or an inhibitor of dopamine metabolism to increase dopamine availability in the cell. Each of the three procedures led to a rapid translocation of dopamine D1 receptors from the cytosol to the plasma membrane.
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            Production of urine free dopamine from DOPA; a micropuncture study.

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              • Article: not found

              General properties and clinical possibilities of new selective inhibitors of catechol O-methyltransferase

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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
                1999
                August 1999
                26 July 1999
                : 7
                : 4
                : 314-322
                Affiliations
                aDepartment of Physiology, University of Uppsala, Biomedical Centre, Uppsala, Sweden; bDepartment of Pharmacology and Toxicology, University of Helsinki, Institute of Biomedicine, Helsinki, Finland
                Article
                20619 Exp Nephrol 1999;7:314–322
                10.1159/000020619
                10450019
                © 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: 5, Tables: 2, References: 41, Pages: 9
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/20619
                Categories
                Original Paper

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