Central role of Rho-kinase in the pathophysiology of allergic asthma Schaafsma, Dedmer

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1 Central role of Rho-kinase in the pathophysiology of allergic asthma Schaafsma, Dedmer IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2007 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Schaafsma, D. (2007). Central role of Rho-kinase in the pathophysiology of allergic asthma s.n. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date:

2 RIJKSUNIVERSITEIT GRONINGEN Central role of Rho-kinase in the pathophysiology of allergic asthma Proefschrift ter verkrijging van het doctoraat in de Wiskunde en Natuurwetenschappen aan de Rijksuniversiteit Groningen op gezag van de Rector Magnificus, dr. F. Zwarts, in het openbaar te verdedigen op vrijdag 2 februari 2007 om uur door Dedmer Schaafsma geboren op 24 maart 1980 te Leeuwarden

3 Promotores Prof. Dr. J. Zaagsma Prof. Dr. H. Meurs Copromotor Dr. S.A. Nelemans Beoordelingscommissie Prof. Dr. A.J. Halayko Prof. Dr. J.G.R. de Mey Prof. Dr. K.F. Rabe ISBN:

4 Paranimfen I.S.T. Bos A.B. Zuidhof The research project described in this thesis was performed within the framework of the Groningen Graduate School for Behavioral and Cognitive Neurosciences (BCN), and the Groningen Research Institute for Asthma and COPD (GRIAC), and was financially supported by a grant from the Netherlands Asthma Foundation (grant 01.83). Printing of this thesis was financially supported by: Groningen Graduate School for Behavioral and Cognitive Neurosciences AstraZeneca BV Boehringer Ingelheim bv Pfizer bv Novartis Pharma BV NV Organon Cover: Immunocytochemistry and photograph by Gerald Stelmack, University of Manitoba, Winnipeg, Canada Copyright 2007 by Dedmer Schaafsma. All rights reserved. No parts of this book may be reproduced in any manner or by any means without the permission from the publisher. Printing: Printpartners Ipskamp B.V., Enschede

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6 Table of contents Contents Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Chapter 7 Chapter 8 Chapter 9 General Intoduction Adapted from: Rho-kinase as a drug target for the treatment of airway hyperresponsiveness in allergic asthma Mini Rev Med Chem (2006) 6: Differential Rho-kinase dependency of full and partial muscarinic receptor agonists in airway smooth muscle contraction Br J Pharmacol (2006) 147: Growth factor-induced contraction of human bronchial smooth muscle is Rho-kinase dependent Eur J Pharmacol (2004) 494:73-76 Role of contractile prostaglandins and Rho-kinase in growth factor-induced airway smooth muscle contraction Respir Res (2005) 6(1):85 Insulin induces airway smooth muscle contraction Br J Pharmacol (2006) In Press Role of Rho-kinase in maintaining airway smooth muscle contractile phenotype Eur J Pharmacol (2004) 483:71-78 Insulin increases the expression of contractile phenotypic markers in airway smooth muscle Submitted (2006) Active allergic sensitization enhances the contribution of Rho-kinase to airway smooth muscle contraction Br J Pharmacol (2004) 143: Inhibition of Rho-kinase normalizes nonspecific hyperresponsiveness in passively sensitized airway smooth muscle preparations Eur J Pharmacol (2006) 531:

7 Table of contents Chapter 10 Inhalation of the Rho-kinase inhibitor Y reverses allergen-induced airway hyper- responsiveness after the early and late asthmatic reaction Respir Res (2006) 7: Chapter 11 Protective effects of the inhaled Rho-kinase inhibitor Y on allergen-induced acute broncho- constriction, airway hyperresponsiveness and inflammation Submitted (2006) 165 Chapter 12 General Discussion and Summary 181 Nederlandse Samenvatting 195 List of abbreviations 203 List of publications 205 Curriculum Vitae 208 Dankwoord 209

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