Abstract
We examined how (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide (Y-27632), an inhibitor of Rho-associated coiled coil-forming protein kinase (ROCK I) and Rho kinase (ROCK II), affects the relaxant responses to beta(2)-adrenoceptor agonists in bovine tracheal smooth muscle preparations precontracted with methacholine. Y-27632 (0.3-30 microM) caused a concentration-dependent attenuation of precontraction with methacholine (0.3-3 microM). Pretreatment with Y-27632 (1 microM) significantly (P<0.05) augmented salbutamol (0.3-100 nM) and terbutaline (0.3 nM-1 microM)-induced relaxations. These results suggest that the ROCK inhibitor could become a new type bronchodilator and its combination with beta(2)-adrenoceptor agonists may become a novel strategy for the long-term treatment of asthma.
MeSH terms
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Adrenergic beta-Agonists / pharmacology*
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Albuterol / pharmacology
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Amides / pharmacology*
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Animals
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Bronchoconstrictor Agents / pharmacology
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Bronchodilator Agents / pharmacology
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Cattle
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Intracellular Signaling Peptides and Proteins
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Methacholine Chloride / pharmacology
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Muscle Relaxants, Central / pharmacology*
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Muscle Relaxation / drug effects*
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Muscle Relaxation / physiology
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Muscle, Smooth / drug effects*
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Muscle, Smooth / physiology
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Pyridines / pharmacology*
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Receptors, Adrenergic, beta-2 / physiology
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Terbutaline / pharmacology
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Trachea / drug effects*
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Trachea / physiology
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rho-Associated Kinases
Substances
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Adrenergic beta-Agonists
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Amides
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Bronchoconstrictor Agents
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Bronchodilator Agents
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Intracellular Signaling Peptides and Proteins
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Muscle Relaxants, Central
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Pyridines
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Receptors, Adrenergic, beta-2
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Methacholine Chloride
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Y 27632
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Protein Serine-Threonine Kinases
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rho-Associated Kinases
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Terbutaline
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Albuterol