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

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.