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      Opioids Hyperpolarize β-Endorphin Neurons via μ-Receptor Activation of a Potassium Conductance

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          Abstract

          Intracellular recordings were made from hypothalamic arcuate (ARC) neurons with biocytin-filled electrodes under current- and voltage-clamp in slices prepared from ovariectomized guinea pigs which were pretreated with estradiol. Forty-three neurons were identified after linking the intracellular biocytin with streptavidin-FΓΓC and subsequently were examined for β-endorphin immunoreactivity. Ten of these neurons were immunoreactive for β-endorphin. β-Endorphin neurons displayed the following passive membrane properties: RMP: –56 ± 2 mV; R<sub>in</sub>: 439 ± 66 MΩ; τ: 17.5 ± 2.4 ms; and often fired spontaneously (5.9 ± 2.2 Hz). These membrane characteristics were not different from identified neurons in the ARC that were not immunoreactive for β-endorphin. β-Endorphin neurons exhibited instantaneous inward rectification and time-dependent rectification. The µ-opioid agonist Tyr-ö-Ala-Gly-MePhe-Gly-ol (DAGO) decreased spontaneous firing, induced membrane hyperpolarization (12 ± 2 mV; range 6–22 mV) and decreased the R<sub>in</sub> (38 ± 4%) of the β-endorphin neurons. These effects of DAGO were blocked by the opioid antagonist naloxone (1 µ M) and were not blocked by 1 µ M TTX. DAGO-responsive cells were unaffected by either ĸ- or δ-receptor opioid agonists. These results indicate that µ-receptors may be autoreceptors on ARC β-endorphin neurons and that activation of opioid µ-receptors hyperpolarizes β-endorphin neurons via an increase in K<sup>+</sup> conductance. Therefore, opioid peptides may modulate opioid tone through an ‘ultra-short loop’ feedback control mechanism.

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          Author and article information

          Journal
          NEN
          Neuroendocrinology
          10.1159/issn.0028-3835
          Neuroendocrinology
          S. Karger AG
          0028-3835
          1423-0194
          1990
          1990
          03 April 2008
          : 52
          : 3
          : 268-275
          Affiliations
          Department of Physiology, Oregon Health Sciences University, Portland, Oreg., USA
          Article
          125597 Neuroendocrinology 1990;52:268–275
          10.1159/000125597
          2170854
          2f790636-ead9-4dba-a9c3-0785728d491a
          © 1990 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
          : 11 October 1989
          : 01 March 1990
          Page count
          Pages: 8
          Categories
          Original Paper

          Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
          Hypothalamus,β-Endorphin,K+ conductance,µ-Opioid receptor,Arcuate,Autoreceptor,Hyperpolarization,Voltage clamp

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