Evaluation of Y-27632, a rho-kinase inhibitor, as a bronchodilator in guinea pigs
| Autor: | Kunio Dobashi, Kunihiko Iizuka, Hideo Tsukagoshi, Takahiro Murozono, Yasuo Shimizu, Tsugio Nakazawa, Masatomo Mori, Takashi Harada, Akihiro Yoshii |
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| Rok vydání: | 2000 |
| Předmět: |
Agonist
Male medicine.medical_specialty medicine.drug_class Pyridines Guinea Pigs Blood Pressure Propranolol Protein Serine-Threonine Kinases Internal medicine Bronchodilator Administration Inhalation medicine Animals Theophylline Enzyme Inhibitors Lung Pharmacology rho-Associated Kinases biology business.industry Intracellular Signaling Peptides and Proteins respiratory system Amides Acetylcholine Bronchodilator Agents Endocrinology Rho kinase inhibitor Enzyme inhibitor Salbutamol biology.protein business medicine.drug Muscle Contraction |
| Zdroj: | European journal of pharmacology. 406(2) |
| ISSN: | 0014-2999 |
| Popis: | 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 beta-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 beta-adrenoceptors. |
| Databáze: | OpenAIRE |
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