Inhibition of Rho-kinase normalizes nonspecific hyperresponsiveness in passively sensitized airway smooth muscle preparations

Autor: Dedmer Schaafsma, Herman Meurs, Annet B. Zuidhof, Johan Zaagsma, S. A. Nelemans
Přispěvatelé: Molecular Pharmacology, Groningen Research Institute for Asthma and COPD (GRIAC)
Jazyk: angličtina
Rok vydání: 2006
Předmět:
Male
Contraction (grammar)
Time Factors
Pyridines
Pharmacology
RESPONSIVENESS
chemistry.chemical_compound
CA2+ SENSITIZATION
Y-27632
HISTAMINE
Enzyme Inhibitors
Rho-associated protein kinase
Sensitization
Methacholine Chloride
rho-Associated Kinases
passive sensitization
Intracellular Signaling Peptides and Proteins
ovalbumin
respiratory system
LEUKOTRIENE C-4
airway smooth muscle
Trachea
medicine.anatomical_structure
MAST-CELLS
medicine.symptom
Histamine
medicine.drug
Muscle contraction
Muscle Contraction
Agonist
(guinea pig)
medicine.drug_class
Guinea Pigs
In Vitro Techniques
Protein Serine-Threonine Kinases
Guinea pig
medicine
Animals
Rho-kinase
TRACHEAL
Dose-Response Relationship
Drug
business.industry
GUINEA-PIGS
airway hyperresponsiveness
contraction
Muscle
Smooth
asthma
allergy
Amides
chemistry
Immunology
Methacholine
business
Zdroj: European Journal of Pharmacology, 531(1-3), 145-150. ELSEVIER SCIENCE BV
ISSN: 0014-2999
Popis: Currently, little is known about mechanisms underlying passive sensitization-induced nonspecific airway hyperresponsiveness. We sought to determine whether the nonspecific airway hyperresponsiveness observed after passive sensitization involves an increased role of Rho-kinase in airway smooth muscle contraction. In addition, the contribution of Rho-kinase to specific allergen-induced airway sinooth muscle contraction was studied. Guinea pig tracheal smooth muscle preparations were incubated for 16 h, in the presence of serum obtained from nonsensitized guinea pigs or atopic serum obtained from actively ovalbumin-sensitized guinea pigs. After incubation, the contribution of Rho-kinase to histamine-, methacholine- or ovalbumin-induced isometric contractions was determined, using the specific Rho-kinase inhibitor Y-27632.Maximal contractions induced by histamine and methacholine were significantly increased in passively sensitized preparations, without a change in potency (-logEC(50)). In control preparations, Y-27632 reduced the potency of both agonists, Without affecting maximal contraction. Remarkably, the increased agonist responsiveness induced by passive sensitization was fully normalized by Y-27632. Treatment with Y-27632 also reduced ovalbumin-induced contraction in these preparations.This study shows that the nonspecific airway smooth muscle hyperresponsiveness as well as the specific allergen responsiveness induced by passive sensitization are dependent on Rho-kinase. The complete inhibition by Y-27632 of the passive sensitization-induced increased responsiveness toward histamine and methacholine indicates a pivotal role of Rho-kinase in this process. (c) 2005 Elsevier B.V. All rights reserved.
Databáze: OpenAIRE
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