HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Brannan, J. D. Articles by Kumlin, M. Search for Related Content PubMed PubMed Citation Articles by Brannan, J. D. Articles by Kumlin, M.

Inhibition of mast cell PGD₂ release protects against mannitol-induced airway narrowing

¹ Dept of Respiratory Medicine, Royal Prince Alfred Hospital, Camperdown, and Depts of ³ Pharmacy and ⁴ Pharmacology, University of Sydney, Sydney, Australia² Division of Physiology, Unit for Experimental Asthma & Allergy Research, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, ⁵ Both authors contributed equally to this study.

CORRESPONDENCE: J. D. Brannan, Dept of Respiratory Medicine, 11 West, Royal Prince Alfred Hospital, Missenden Road, Camperdown NSW 2050, Australia. Fax: 61 295158196. E-mail: johnb{at}med.usyd.edu.au

Keywords: Cromoglycate, formoterol, leukotriene E₄, mannitol, 9, 11ß-prostaglandin F₂

Received: July 4, 2005
Accepted December 16, 2005

Mannitol inhalation increases urinary excretion of 9,11ß-prostaglandin F₂ (a metabolite of prostaglandin D₂ and marker of mast cell activation) and leukotriene E₄. The present study tested the hypothesis that ß₂-adrenoreceptor agonists and disodium cromoglycate (SCG) protect against mannitol-induced bronchoconstriction by inhibition of mast cell mediator release.

Fourteen asthmatic subjects inhaled mannitol (mean dose 252±213 mg) in order to induce a fall in forced expiratory volume in one second (FEV₁) of 25%. The same dose was given 15 min after inhalation of formoterol fumarate (24 µg), SCG (40 mg) or placebo. Pre- and post-challenge urine samples were analysed by enzyme immunoassay for 9,11ß-prostaglandin F₂ and leukotriene E₄.

The maximum fall in FEV₁ of 32±10% on placebo was reduced by 95% following formoterol and 63% following SCG. Following placebo, there was an increase in median urinary 9,11ß-prostaglandin F₂ concentration from 61 to 92 ng·mmol creatinine^–1, but no significant increase in 9,11ß-prostaglandin F₂ concentration in the presence of either formoterol (69 versus 67 ng·mmol creatinine^–1) or SCG (66 versus 60 ng·mmol creatinine^–1). The increase in urinary leukotriene E₄ following placebo (from 19 to 31 ng·mmol creatinine^–1) was unaffected by the drugs.

These results support the hypothesis that the drug effect on airway response to mannitol is due to inhibition of mast cell prostaglandin D₂ release.

This article has been cited by other articles:

				A. Jaques, E. Daviskas, J. A. Turton, K. McKay, P. Cooper, R. G. Stirling, C. F. Robertson, P. T. P. Bye, P. N. LeSouef, B. Shadbolt, et al. Inhaled Mannitol Improves Lung Function in Cystic Fibrosis Chest, June 1, 2008; 133(6): 1388 - 1396. [Abstract] [Full Text] [PDF]