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 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 × 10⁻⁶M. Y-27632 also dose-dependently relaxed the bronchi precontracted by acetylcholine (ACh), histamine and neurokinin A, and the IC₅₀was 3.0 ± 0.4 × 10⁻⁶, 2.5 ± 0.5 × 10⁻⁶and 1.8 ± 0.3 × 10⁻⁶M, 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 (IC₅₀= 1.6 ± 0.1 × 10⁻⁶M). These data suggest that Y-27632 has a dilatory capacity on human bronchi as well as on pulmonary arteries.