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This Article Full Text Full Text (PDF) All Versions of this Article: 290/1/L179    most recent 00330.2005v1 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 (4) Citing Articles via Google Scholar Google Scholar Articles by Papapetropoulos, A. Articles by Gratziou, C. Search for Related Content PubMed PubMed Citation Articles by Papapetropoulos, A. Articles by Gratziou, C.

Soluble guanylyl cyclase expression is reduced in allergic asthma

¹"G. P. Livanos and M. Simou" Laboratories, Evangelismos Hospital, Department of Critical Care and Pulmonary Services, University of Athens School of Medicine, Athens; ²Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, Patras; and ³Center for Immunology and Transplantation, Institute for Biomedical Research, Academy of Athens, Athens, Greece

Submitted 26 July 2005 ; accepted in final form 27 August 2005

Soluble guanylyl cyclase (sGC) is an enzyme highly expressed in the lung that generates cGMP contributing to airway smooth muscle relaxation. To determine whether the bronchoconstriction observed in asthma is accompanied by changes in sGC expression, we used a well-established murine model of allergic asthma. Histological and biochemical analyses confirmed the presence of inflammation in the lungs of mice sensitized and challenged with ovalbumin (OVA). Moreover, mice sensitized and challenged with OVA exhibited airway hyperreactivity to methacholine inhalation. Steady-state mRNA levels for all sGC subunits (1, 2, and 1) were reduced in the lungs of mice with allergic asthma by 60–80%, as estimated by real-time PCR. These changes in mRNA were paralleled by changes at the protein level: 1, 2, and 1 expression was reduced by 50–80% as determined by Western blotting. Reduced 1 and 1 expression in bronchial smooth muscle cells was demonstrated by immunohistochemistry. To study if sGC inhibition mimics the airway hyperreactivity seen in asthma, we treated naïve mice with a selective sGC inhibitor. Indeed, in mice receiving ODQ the methacholine dose response was shifted to the left. We conclude that sGC expression is reduced in experimental asthma contributing to the observed airway hyperreactivity.

nitric oxide; guanosine 3',5'-cyclic monophosphate, airway hyperreactivity; bronchoconstriction

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