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      Influence of Uptake 1 and Uptake 2 on the Relationship between Diffusion and Metabolism of Noradrenaline in the Perfused Rabbit Ear Artery

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          Abstract

          <sup>3</sup>H-metabolite effluxes from each surface of the perfused rabbit ear artery were measured during a 30-min period of application of <sup>3</sup>H-(–)-noradrenaline (NA) to the intimal surface, the adventitial surface, and both surfaces simultaneously. The arteries were from reserpine-treated rabbits and were perfused in Ca-free medium containing prazosin to prevent the constrictor activity of NA. During intimal application, <sup>3</sup>H-normetanephrine (NMN) was the principal metabolite. Effects of hydrocortisone, and of cocaine, indicated that (a) <sup>3</sup>H-NMN was derived largely via uptake2, (b) <sup>3</sup>H-3,4-dihydroxyphenylethylene glycol (DOPEG) was derived largely via uptake<sub>1</sub>, and (c) uptake<sub>2</sub> limited access of the NA to sites of uptake<sub>1 </sub>During adventitial application, <sup>3</sup>H-DOPEG was the principal metabolite. Effects of cocaine and hydrocortisone indicated that (a) <sup>3</sup>H-DOPEG was derived largely via uptake<sub>1</sub>, (b) <sup>3</sup>H-NMN was only partly derived via uptake<sub>2</sub>, and (c) uptake<sub>1</sub> limited access of the NA to sites of uptake<sub>2 </sub>When <sup>3</sup>H-NA entered both surfaces simultaneously, the effluxes of the deaminated catechols were identical to those prevailing during adventitial entry of the amine. In contrast, the effluxes of NMN corresponded more closely to the sum of those prevailing during entry via each surface separately. It is suggested that, in the perfused artery, regional differences in the diffusivity of NA between the adventitia and media are primarily responsible for the marked influence which the surface of entry exerts on exogenous NA metabolism.

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          Author and article information

          Journal
          JVR
          J Vasc Res
          10.1159/issn.1018-1172
          Journal of Vascular Research
          S. Karger AG
          1018-1172
          1423-0135
          1988
          1988
          23 September 2008
          : 25
          : 5
          : 217-231
          Affiliations
          Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia
          Article
          158734 Blood Vessels 1988;25:217–231
          10.1159/000158734
          © 1988 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: 15
          Categories
          Research Paper

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