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      Increased Rate of Adenine Incorporation into Adenine Nucleotide Pool in Erythrocytes of Patients with Chronic Renal Failure

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          Abstract

          Background: Elevated purine nucleotide pool (mainly ATP) in erythrocytes of patients with chronic renal failure (CRF) is a known phenomenon, however the mechanism responsible for this abnormality is far from being clear. We hypothesize that the increased rate of adenine incorporation into adenine nucleotide pool is responsible for the elevated level of ATP in uremic erythrocytes. Methods: In chronically uremic patients we evaluated using HPLC technique: (a) plasma adenine concentration; (b) the rate of adenine incorporation into adenine nucleotide pool in uremic erythrocytes. Additionally, the effect of higher than physiological phosphate concentration (2.4 m M) and lower than physiological pH (7.1) on adenine incorporation into erythrocytes adenine nucleotide pool was investigated. Healthy volunteers with normal renal function served as control. Results: The concentration of adenine in plasma of CRF patients was found to be significantly higher than in plasma of healthy subjects. In contrast, adenosine concentration was similar both in healthy humans and in CRF patients. In isolated erythrocytes of uremic patients (incubated in the medium pH 7.4, containing 1.2 m M inorganic phosphate) adenine was incorporated into adenine nucleotide pool at a rate approximately 2-fold higher than in erythrocytes from healthy subjects. The rate of adenosine incorporation into adenine nucleotide pool was similar in erythrocytes of both studied groups. Incubation of erythrocytes obtained from healthy subjects in the medium pH 7.4, containing 2.4 m M inorganic phosphate, caused the increase of adenine incorporation into adenine nucleotide pool by about 60%. Incubation of the cells in the pH 7.1 buffer containing 2.4 m M inorganic phosphate increased the rate of adenine incorporation into adenylate approximately 2-fold as compared to erythrocytes incubated in the medium pH 7.4 containing 1.2 m M inorganic phosphate. Erythrocytes obtained from uremic patients and incubated in the pH 7.1 medium containing 2.4 m M phosphate incorporated adenine into adenine nucleotide pool at a rate similar to erythrocytes incubated in the medium pH 7.4 containing 1.2 m M phosphate. Erythrocytes obtained from either healthy subjects or from patients with CRF and incubated in the presence of higher than physiological concentration of inorganic phosphate (2.4 m M) and lower than physiological pH (7.1) did not exhibit any increase in the rate of adenisine incorporation into adenine nucleotide pool. Conclusion: These results suggest that the increased rate of adenine incorporation into adenine nucleotide pool could be partially responsible for the increased concentration of ATP in uremic erythrocytes.

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          Direct resolution of the optical isomers of fenoldopam and one of its derivatives

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            Author and article information

            Journal
            NEF
            Nephron
            10.1159/issn.1660-8151
            Nephron
            S. Karger AG
            1660-8151
            2235-3186
            2000
            November 2000
            08 November 2000
            : 86
            : 3
            : 281-286
            Affiliations
            Departments of aBiochemistry and bNephrology, Medical University of Gdańsk, Poland
            Article
            45782 Nephron 2000;86:281–286
            10.1159/000045782
            11096284
            66d520b5-3490-45cd-8787-5a1ec8d52bde
            © 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.

            History
            Page count
            Figures: 2, References: 40, Pages: 6
            Categories
            Original Paper

            Cardiovascular Medicine,Nephrology
            Adenine nucleotide,Chronic renal failure,Adenine,ATP,Human Erythrocyte

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