CysLT receptor activation is involved in LTC-induced lung air-trapping in guinea pigs.

CysLT receptors are known to be involved in the pathogenesis of asthma. However, the functional roles of CysLT receptors in this condition have not been determined. The purpose of this study is to develop an experimental model of CysLT receptor-mediated LTC-induced lung air-trapping in guinea pigs and use this model to clarify the mechanism underlying response to such trapping. Because LTC is rapidly converted to LTD by γ-glutamyltranspeptidase (γ-GTP) under physiological conditions, S-hexyl GSH was used as a γ-GTP inhibitor. In anesthetized artificially ventilated guinea pigs with no S-hexyl GSH treatment, i.v. LTC-induced bronchoconstriction was almost completely inhibited by montelukast, a CysLT receptor antagonist, but not by BayCysLTRA, a CysLT receptor antagonist. The inhibitory effect of montelukast was diminished by treatment with S-hexyl GSH, whereas the effect of BayCysLTRA was enhanced with increasing dose of S-hexyl GSH. Macroscopic and histological examination of lung tissue isolated from LTC-/S-hexyl-GSH-treated guinea pigs revealed air-trapping expansion, particularly at the alveolar site. Inhaled LTC in conscious guinea pigs treated with S-hexyl GSH increased both airway resistance and airway hyperinflation. On the other hand, LTC-induced air-trapping was only partially suppressed by treatment with the bronchodilator salmeterol. Although montelukast inhibition of LTC-induced air-trapping was weak, treatment with BayCysLTRA resulted in complete suppression of this air-trapping. Furthermore, BayCysLTRA completely suppressed LTC-induced airway vascular hyperpermeability. In conclusion, we found in this study that CysLT receptors mediate LTC-induced bronchoconstriction and air-trapping in S-hexyl GSH-treated guinea pigs. It is therefore believed that CysLT receptors contribute to asthmatic response involving air-trapping.