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Table of Contents
Vol. 130, No. 3, 2003
Issue release date: March 2003
Section title: Original Paper
Int Arch Allergy Immunol 2003;130:224–231
(DOI:10.1159/000069516)

Acute Stress Results in Skin Corticotropin-Releasing Hormone Secretion, Mast Cell Activation and Vascular Permeability, an Effect Mimicked by Intradermal Corticotropin-Releasing Hormone and Inhibited by Histamine-1 Receptor Antagonists

Lytinas M. · Kempuraj D. · Huang M. · Boucher W. · Esposito P. · Theoharides T.C.
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Mass., USA

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: July 04, 2002
Accepted: December 19, 2002
Published online: April 02, 2003
Issue release date: March 2003

Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 1

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: http://www.karger.com/IAA

Abstract

Background: Mast cells play an important role in allergic inflammation by releasing vasoactive molecules, proteases and cytokines. Corticotropin-releasing hormone (CRH) and its structural analogue urocortin (Ucn) were shown to trigger skin mast cell activation and vascular permeability. We investigated the effect of acute stress on rat skin vascular permeability and CRH secretion, as well as the effect of intradermal CRH, and that of two histamine-1 receptor antagonists, azelastine and olopatadine, on vascular permeability. Methods: Rats were stressed by restraint and vascular permeability was assessed by extravasation of 99Tc-gluceptate, while mast cell activation was determined by skin rat mast cell protease-1 (RMCP-1) content. Skin CRH content was evaluated by ELISA. The effect of intradermal injection of CRH and Ucn, as well as that of two histamine-1 receptor antagonists, azelastine and olopatadine, was assessed by Evan’s blue extravasation. Purified rat peritoneal mast cells (RPMCs) were also pretreated with azelastine (24 µM) or olopatadine (133 µM) for 5 min before challenge with compound 48/80 (0.5 µg/ml) for 30 min. Histamine secretion was measured fluorometrically. Intracellular Ca2+ ions were evaluated in RPMCs loaded with calcium crimson and stimulated with compound 48/80. Results: Acute stress increased skin vascular permeability and CRH content, while it decreased RMCP-1. Intradermal injection of CRH or Ucn induced substantial Evan’s blue extravasation that was inhibited by pretreatment with azelastine (24 µM) and olopatadine (133 µM). Both antihistamines also inhibited histamine release and intracellular increase of Ca2+ ions from RPMCs stimulated by compound 48/80. Conclusions: These results indicate that acute stress increases skin CRH that can trigger mast cell-dependent vascular permeability, effects inhibited by certain histamine-1 receptor antagonists, possibly acting to reduce intracellular Ca2+ ion levels.

© 2003 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: July 04, 2002
Accepted: December 19, 2002
Published online: April 02, 2003
Issue release date: March 2003

Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 1

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: http://www.karger.com/IAA


Copyright / Drug Dosage / Disclaimer

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 or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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.
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