Effect of a calcium sensitization modulator, Y-27632, on isolated human bronchus and pulmonary artery

Shunsuke Yamagata, Masakazu Ichinose, Hisatoshi Sugiura, Akira Koarai, Kaoru Koike, Kunio Shirato

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20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)25-29
Number of pages5
JournalPulmonary Pharmacology and Therapeutics
Volume13
Issue number1
DOIs
Publication statusPublished - 2000 Feb

Keywords

  • Bronchial asthma
  • Bronchial dilation
  • Cholinergic nerve
  • Human tissues
  • Pulmonary vasodilation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Biochemistry, medical
  • Pharmacology (medical)

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