TY - JOUR
T1 - Effect of a calcium sensitization modulator, Y-27632, on isolated human bronchus and pulmonary artery
AU - Yamagata, Shunsuke
AU - Ichinose, Masakazu
AU - Sugiura, Hisatoshi
AU - Koarai, Akira
AU - Koike, Kaoru
AU - Shirato, Kunio
N1 - Funding Information:
∗ Author for correspondence: Masakazu Ichinose, M.D., First Department of Internal Medicine, Tohoku University School of Medicine 1–1, Seiryo-machi, Aoba-ku, Sendai 980–8574, Japan. Fax: 81–22–717–7156. E-mail: ichinose@int1.med.tohoku.ac.jp Supported by Science Research Grant 10470148 from the Ministry of Education, Science, Sports, and Culture of Japan.
PY - 2000/2
Y1 - 2000/2
N2 - A recently developed pyridine derivative, Y-27632, has been reported to inhibit smooth muscle contraction by inhibiting Ca2+ 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 IC50 (concentration causing 50% relaxation of the maximal response) of 2.0 ± 0.3 x 106 M. Y-27632 also dose-dependently relaxed the bronchi precontracted by acetylcholine (ACh), histamine and neurokinin A, and the IC50 was 3.0 ± 0.4 x 106, 2.5 ± 0.5 x 106 and 1.8 ± 0.3 x 106 M, respectively. The dilator, 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 (IC50 = 1.6 ± 0.1 x 106 M). These data suggest that Y-27632 has a dilatory capacity on human bronchi as well as on pulmonary arteries. (C) 2000 Academic Press.
AB - A recently developed pyridine derivative, Y-27632, has been reported to inhibit smooth muscle contraction by inhibiting Ca2+ 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 IC50 (concentration causing 50% relaxation of the maximal response) of 2.0 ± 0.3 x 106 M. Y-27632 also dose-dependently relaxed the bronchi precontracted by acetylcholine (ACh), histamine and neurokinin A, and the IC50 was 3.0 ± 0.4 x 106, 2.5 ± 0.5 x 106 and 1.8 ± 0.3 x 106 M, respectively. The dilator, 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 (IC50 = 1.6 ± 0.1 x 106 M). These data suggest that Y-27632 has a dilatory capacity on human bronchi as well as on pulmonary arteries. (C) 2000 Academic Press.
KW - Bronchial asthma
KW - Bronchial dilation
KW - Cholinergic nerve
KW - Human tissues
KW - Pulmonary vasodilation
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U2 - 10.1006/pupt.1999.0227
DO - 10.1006/pupt.1999.0227
M3 - Article
C2 - 10718987
AN - SCOPUS:0034112234
VL - 13
SP - 25
EP - 29
JO - Pulmonary Pharmacology and Therapeutics
JF - Pulmonary Pharmacology and Therapeutics
SN - 1094-5539
IS - 1
ER -