0
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Effects of Luteinizing-Hormone-Releasing Hormone, α-Melanocyte-Stimulating Hormone, Naloxone, Dexamethasone and Indomethacin on lnterleukin-2-lnduced Corticotropin-Releasing Factor Release

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Our previous studies have shown that the microinjection of interleukin (IL)-2 into the third ventricle of conscious rats evokes the release of adrenocorticotropin hormone (ACTH) and that its incubation with hemipituitaries in vitro was also effective in releasing ACTH. In the present experiments, we evaluated the effect of IL-2 on the release of corticotropin-releasing factor (CRF) from medial basal hypothalami (MBHs) incubated in vitro and studied the effect of other agents, whose release is altered in stress, on CRF release. IL-2 significantly stimulated CRF release at concentrations of 10<sup>–13</sup> and 10<sup>–14</sup> M, whereas increasing the concentration to 10<sup>–12</sup> to 10<sup>–10</sup> M did not produce significant release of CRF. A high concentration of potassium (55 m M) in the medium also significantly stimulated CRF release and this stimulation was not modified by IL-2. Since high-potassium-induced release of CRF is probably due to opening of voltage-dependent calcium channels, it is likely that IL-2 is releasing CRF by this mechanism. Since the release of luteinizing-hormone-releasing hormone (LHRH) is modified by stress, we evaluated the action of LHRH on CRF release and the release induced by IL-2. Although LHRH failed to alter basal CRF release, except for a slight decrease at 10<sup>–7</sup> M, it completely blocked IL-2-induced CRF release at this concentration. To examine a possible role for opioid peptides in CRF release, the opiate receptor blocker, naloxone (NAL), was tested. At concentrations of 5 × 10<sup>–6</sup> and 10<sup>–5</sup> M, it produced a marked increase in CRF release; however, the simultaneous exposure of MBHs to each of these concentrations of NAL plus IL-2 caused a dose-dependent decrease in IL-2-induced CRF release, suggesting that β-endorphin or other opioid peptides may play a role in IL-2-induced CRF release. As has been previously shown for IL-1 and IL-6, IL-2-induced CRF release was blocked by α-melanocyte-stimulating hormone (α-MSH), which at high concentrations also reduced basal CRF release. As in the case of IL-1 and IL-2, dexamethasone (DEX), the highly active synthetic glucocorticoid, although not altering basal CRF release, completely blocked the response to IL-2. The inhibitor of cyclo-oxygenase, indomethacin (IND), also blocked IL-2-induced CRF release just as it has previously been shown to block IL-1- and IL-6-induced CRF release. The results are consistent with the hypothesis that IL-2 acts on its recently discovered receptors to induce an increase in intracellular calcium. In other experiments, we have shown that this activates nitric oxide (NO) synthase leading to production of NO by a NOergic neuron. NO diffuses to the CRF neuron and activates cyclo-oxygenase leading to generation of prostaglandin E<sub>2</sub>, which activates adenylate cyclase and increases cyclic AMP release, which then causes extrusion of CRF secretory granules. DEX presumably acts on its receptors on the CRF neuron to inhibit the increase in intracellular calcium and thereby blocks activation of phospholipase A<sub>2</sub> necessary for activation of the arachidonic acid cascade. α-MSH and LHRH may similarly act on their receptors on these cells to, in some manner, block the pathway. On the other hand, β-endorphin and/or other opioid peptides inhibit the pathway. Further experiments will be necessary to elucidate the exact points in the pathway at which these compounds are effective.

          Related collections

          Author and article information

          Journal
          NIM
          Neuroimmunomodulation
          10.1159/issn.1021-7401
          Neuroimmunomodulation
          S. Karger AG
          1021-7401
          1423-0216
          1995
          1995
          20 November 1995
          : 2
          : 3
          : 166-173
          Affiliations
          Department of Physiology, Neuropeptide Division, The University of Texas Southwestern Medical Center at Dallas, Tex., USA
          Article
          96888 Neuroimmunomodulation 1995;2:166–173
          10.1159/000096888
          8646567
          © 1995 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: 8
          Categories
          Original Paper

          Comments

          Comment on this article