Determination of Histamine in Microdialysis Samples from Guinea Pig Skin by High-Performance Liquid Chromatography with Fluorescence Detection

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Abstract

Aim: To develop a sensitive and selective liquid-chromatographic method for the determination of histamine in microdialysis samples from guinea pig skin following allergenic provocation. Methods: The novel fluorescence derivatization method is based on an intramolecular excimer-forming reaction between 2 amino moieties of histamine and 2 molecules of 4-(1-pyrene)butanoyl chloride (PBC) yielding the corresponding dipyrene-labeled derivative. Results: The PBC derivative of histamine was separated within 20 min, and the detection limit (signal-to-noise ratio = 3) of histamine was 0.6 fmol/20 µl volume injected. The basal extracellular levels of histamine in guinea pig skin microdialysates were 20.6 ± 1.7 fmol/10 µl. Subcutaneous administration of histamine liberator compound 48/80 (3 mg/kg) increased the extracellular histamine levels in the skin dialysates by about 860%, whereas ovalbumin challenge (2 mg/kg i.v.) in the sensitized guinea pigs increased the extracellular histamine levels by about 3,030%. Conclusion: The novel technique for histamine determination in microdialysis samples from the guinea pig skin may be utilized in preclinical research of antihistaminergic drugs and evaluation of allergenic properties of various dermal preparations such as transdermal drug delivery systems.

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Acute effects of substance P and calcitonin gene-related peptide in human skin--a microdialysis study.

C Weidner, M Klede, R Rukwied … (2000)

Upon activation nociceptors release neuropeptides in the skin provoking vasodilation and plasma protein extravasation in rodents, but only vasodilation in humans. Pivotal peptides in the induction of neurogenic inflammation comprise calcitonin gene-related peptide and substance P, the latter being suggested to act partly via degranulation of mast cells. In this study substance P and calcitonin gene-related peptide-induced vasodilation, protein extravasation, histamine release, and sensory effects were investigated simultaneously in human skin by dermal microdialysis. The vasodilatory prostaglandin E(2) and the mast cell activator codeine served as positive controls. Substance P and calcitonin gene-related peptide applied intradermally via large cut-off plasmapheresis capillaries induced dose-dependent local vasodilation, but only SP provoked protein extravasation in concentrations greater than 10(-9) M. Substance P-induced (10(-8)-10(-6) M) protein extravasation was not accompanied by histamine release and was unaffected by cetirizine (histamine H1 blocker, 200 microg per ml). Only the highest concentration of substance P (10(-5) M) induced significant histamine release. Neither neuropeptide caused any axon reflex erythema or any itch or pain sensation, whereas mast cell degranulation by codeine dose dependently provoked itch, flare, protein extravasation, and histamine release. In human skin calcitonin gene-related peptide and substance P induce vasodilation by a mechanism not involving histamine. No evidence for neuropeptide-induced activation of nociceptors was obtained. Our results suggest that endogenous calcitonin gene-related peptide and substance P have no acute sensory function in human skin. The lack of neurogenic protein extravasation in humans can most probably be attributed to low local concentrations of this neuropeptide still sufficient to exert trophic and immunomodulatory effects (10(-11) M), but too low to induce protein extravasation (10(-8) M) or even mast cell degranulation (10(-5) M). J Invest Dermatol 115:1015-1020 2000

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Chemical response pattern of different classes of C-nociceptors to pruritogens and algogens.

Erwin R. Schmidt, Eva Schmelz, H E Torebjörk … (2003)

Vasoneuroactive substances were applied through intradermal microdialysis membranes and characterized as itch- or pain-inducing in psychophysical experiments. Histamine always provoked itching and rarely pain, capsaicin always pain but never itching. Prostaglandin E(2) (PGE(2)) led preferentially to moderate itching. Serotonin, acetylcholine, and bradykinin induced pain more often than itching. Subsequently the same substances were used in microneurography experiments to characterize the sensitivity profile of human cutaneous C-nociceptors. The responses of 89 mechanoresponsive (CMH, polymodal nociceptors), 52 mechanoinsensitive, histamine-negative (CMi(His-)), and 24 mechanoinsensitive, histamine-positive (CMi(His+)) units were compared. CMi(His+) units were most responsive to histamine and to PGE(2) and less to serotonin, ACh, bradykinin, and capsaicin. CMH units (polymodal nociceptors) and CMi(His-) units showed significantly weaker responses to histamine, PGE(2), and acetylcholine. Capsaicin and bradykinin responses were not significantly different in the two classes of mechano-insensitive units. We conclude that CMi(His+) units are "selective," but not "specific" for pruritogenic substances and that the pruritic potency of a mediator increases with its ability to activate CMi(His+) units but decreases with activation of CMH and CMi(His-) units.

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The role of histamine in allergic diseases

M. White (1990)

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Author and article information

Journal

Journal ID (publisher-id): SPP

Journal ID (nlm-ta): Skin Pharmacol Physiol

Journal ID (doi): 10.1159/issn.1660-5527

Title: Skin Pharmacology and Physiology

Publisher: S. Karger AG

ISSN (Print): 1660-5527

ISSN (Electronic): 1660-5535

Publication date Subscription-year: 2012

Publication date (Print): February 2012

Publication date (Electronic): 05 October 2011

Volume: 25

Issue: 2

Pages: 65-72

Affiliations

^aDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; ^bSchool of Pharmacy, International University of Health and Welfare, Tochigi, and ^cFaculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan

Author notes

*Prof. Takashi Yoshitake, Department of Physiology and Pharmacology, Karolinska Institutet, Nanna Svartz vag 2, SE–171 77 Stockholm (Sweden), Tel. +46 85 248 7990, E-Mail takashi.yoshitake@ki.se

Article

Publisher ID: 330899 Other ID: Skin Pharmacol Physiol 2012;25:65–72

DOI: 10.1159/000330899

PubMed ID: 21986353

SO-VID: cfe5201e-9ea3-4e27-91e3-89c9e1f99325

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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

Date received : 31 March 2011

Date accepted : 23 June 2011

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Figures: 6, Pages: 8

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Determination of Histamine in Microdialysis Samples from Guinea Pig Skin by High-Performance Liquid Chromatography with Fluorescence Detection

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Abstract

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Karger: Dermatology

Most cited references 31

Acute effects of substance P and calcitonin gene-related peptide in human skin--a microdialysis study.

Chemical response pattern of different classes of C-nociceptors to pruritogens and algogens.

The role of histamine in allergic diseases

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