Evaluation of Y-27632, a Rho-kinase inhibitor, as a bronchodilator in guinea pigs

To evaluate (+)-( R)- trans-4-(l-Aminoethyl)- N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride, monohydrate (Y-27632), a selective Rho-kinase inhibitor, as a novel bronchodilator in vivo and in vitro, we investigated the effect of Y-27632 on the acetylcholine- or ovalbumin-induced increase in lu...

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Bibliographic Details
Published in:European journal of pharmacology 2000-10, Vol.406 (2), p.273-279
Main Authors: Iizuka, Kunihiko, Shimizu, Yasuo, Tsukagoshi, Hideo, Yoshii, Akihiro, Harada, Takashi, Dobashi, Kunio, Murozono, Takahiro, Nakazawa, Tsugio, Mori, Masatomo
Format: Article
Language:English
Subjects:
Acetylcholine - pharmacology
Administration, Inhalation
Amides - pharmacology
Animals
Biological and medical sciences
Blood Pressure - drug effects
Bronchodilator
Bronchodilator Agents - pharmacology
Enzyme Inhibitors - pharmacology
Guinea Pigs
Intracellular Signaling Peptides and Proteins
Lung - drug effects
Male
Medical sciences
Muscle Contraction - drug effects
Pharmacology. Drug treatments
Protein-Serine-Threonine Kinases - antagonists & inhibitors
Pyridines - pharmacology
Respiratory system
rho-Associated Kinases
Rho-kinase
Y-27632
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Summary:To evaluate (+)-( R)- trans-4-(l-Aminoethyl)- N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride, monohydrate (Y-27632), a selective Rho-kinase inhibitor, as a novel bronchodilator in vivo and in vitro, we investigated the effect of Y-27632 on the acetylcholine- or ovalbumin-induced increase in lung resistance ( R L) in non-sensitized or passively sensitized guinea pigs, and the relaxant effects of salbutamol, Y-27632 and theophylline on acetylcholine- or ovalbumin-induced contraction of isolated trachea. Y-27632 inhalation (1 mM, 2 min) inhibited acetylcholine- or ovalbumin-induced increase in R L without changes in mean blood pressure, and the effect persisted for at least 3 h. Salbutamol, Y-27632 and theophylline each completely reversed the acetylcholine- or ovalbumin-induced contraction of isolated trachea with rank order of potency, salbutamol>Y-27632>theophylline. The relaxant effect of Y-27632 was not affected by propranolol. We conclude that, although Y-27632 is not as potent as a β-adrenoceptor agonist, Y-27632 may become an alternative inhaled bronchodilator, because Y-27632 is more potent than theophylline, and the relaxant effect is independent of β-adrenoceptors.
ISSN:0014-2999
1879-0712
DOI:10.1016/S0014-2999(00)00504-5