title: Effect of a calcium sensitization modulator, Y-27632, on isolated human bronchus and pulmonary artery.
abstract: A recently developed pyridine derivative, Y-27632, has been reported to inhibit smooth muscle contraction by inhibiting Ca(2+)sensitization in animal experiments. However, the effect of this compound in human tissues has not yet been elucidated. The aim of the present study was to evaluate the effect of Y-27632 on human bronchi and pulmonary arteries. The tissues were obtained from lung cancer patients undergoing lung resection. Tissue responses were assessed by isometric tension measurement. Y-27632 relaxed the bronchi at basal tone with an IC(50)(concentration causing 50% relaxation of the maximal response) of 2.0+/-0.3x10(-6)M. Y-27632 also dose-dependently relaxed the bronchi precontracted by acetylcholine (ACh), histamine and neurokinin A, and the IC(50)was 3.0+/-0.4x10(-6), 2.5+/-0.5x10(-6)and 1.8 +/-0.3x10(-6)M, respectively. The dilatory effect of Y-27632 was significantly smaller in ACh-precontracted tissues compared with those of basal or histamine- and neurokinin A-induced precontracted bronchi (P<0.05). Further, Y-27632 showed an inhibitory effect on cholinergic nerve stimulation- and ACh-induced bronchial contraction to the same degree, suggesting that a modulatory effect of this compound on ACh release from nerve terminals was unlikely. Y-27632 also dilated the pulmonary arteries precontracted by phenylephrine (IC(50)= 1.6+/-0.1x10(-6)M). These data suggest that Y-27632 has a dilatory capacity on human bronchi as well as on pulmonary arteries.
authors.affiliation: First Department of Internal Medicine, Tohoku University School of Medicine.
authors.forename: S
authors.initials: S
authors.lastname: Yamagata
authors.forename: M
authors.initials: M
authors.lastname: Ichinose
authors.forename: H
authors.initials: H
authors.lastname: Sugiura
authors.forename: A
authors.initials: A
authors.lastname: Koarai
authors.forename: K
authors.initials: K
authors.lastname: Koike
authors.forename: K
authors.initials: K
authors.lastname: Shirato
mesh_terms: D000577:Amides / Q000494:pharmacology* / Q000627:therapeutic use; D000704:Analysis of Variance; D001249:Asthma / Q000517:prevention & control*; D001980:Bronchi / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D009125:Muscle Relaxants, Central / Q000494:pharmacology* / Q000627:therapeutic use; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011651:Pulmonary Artery / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000577:Amides; D009125:Muscle Relaxants, Central; D011725:Pyridines; C108830:Y 27632