Y-27632 potentiates relaxant effects of beta 2-adrenoceptor agonists in bovine tracheal smooth muscle.
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.
Nakahara
T
T
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo, Japan. nakaharat@pharm.kitasato-u.ac.jp
Moriuchi
H
H
Yunoki
M
M
Sakamato
K
K
Ishii
K
K
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology; D002417:Cattle; D047908:Intracellular Signaling Peptides and Proteins; D016210:Methacholine Chloride / Q000494:pharmacology; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology*; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology; D013726:Terbutaline / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology; D054460:rho-Associated Kinases
D000318:Adrenergic beta-Agonists; D000577:Amides; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D047908:Intracellular Signaling Peptides and Proteins; D009125:Muscle Relaxants, Central; D011725:Pyridines; D018343:Receptors, Adrenergic, beta-2; D016210:Methacholine Chloride; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D013726:Terbutaline; D000420:Albuterol