Sekioka Tomohiko, Kadode Michiaki, Fujii Masanori, Kawabata Kazuhito, Abe Takashi, Horiba Michiaki, Kohno Shigekatsu, Nabe Takeshi
Discovery Research Laboratories II, Department of Biology & Pharmacology, Ono Pharmaceutical Co., Ltd., Osaka, Japan; Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto, Japan.
Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto, Japan.
Allergol Int. 2015 Oct;64(4):351-8. doi: 10.1016/j.alit.2015.04.008. Epub 2015 Jun 3.
The expression and functional role of CysLT2 receptors in asthma have not been clarified. In this study, we evaluated CysLT2 receptors expression, and effects of CysLT2-and CysLT1/2-receptor antagonists on antigen-induced bronchoconstriction using isolated lung tissues from both asthma and non-asthma subjects.
CysLT1 and CysLT2 receptors expression in asthma and non-asthma lung tissue preparations was examined in immunohistochemistry experiments, and their functional roles in antigen-induced bronchoconstriction were assessed using ONO-6950, a dual CysLT1/2-receptor antagonist, montelukast, a CysLT1 receptor antagonist, and BayCysLT2RA, a CysLT2 receptor-specific antagonist.
CysLT1 receptors were expressed on the bronchial smooth muscle and epithelium, and on alveolar leukocytes in 5 in 5 non-asthma subjects and 2 in 2 asthma subjects. On the other hand, although degrees of CysLT2 receptors expression were variable among the 5 non-asthma subjects, the expression in the asthma lung was detected on bronchial smooth muscle, epithelium and alveolar leukocytes in 2 in 2 asthma subjects. In the non-asthma specimens, antagonism of CysLT2 receptors did not affect antigen-induced bronchial contractions, even after pretreatment with the CysLT1-receptor specific antagonist, montelukast. However, in the bronchus isolated from one of the 2 asthma subjects, antagonism of CysLT2 receptors suppressed contractions, and dual antagonism of CysLT1 and CysLT2 receptors resulted in additive inhibitory effect on anaphylactic contractions.
CysLT2 receptors were expressed in lung specimens isolated from asthma subjects. Activation of CysLT2 receptors may contribute to antigen-induced bronchoconstriction in certain asthma population.
半胱氨酰白三烯2（CysLT2）受体在哮喘中的表达及功能作用尚未明确。在本研究中，我们使用哮喘和非哮喘受试者的离体肺组织，评估了CysLT2受体的表达，以及CysLT2受体拮抗剂和CysLT1/2受体拮抗剂对抗原诱导的支气管收缩的影响。
在免疫组织化学实验中检测哮喘和非哮喘肺组织标本中CysLT1和CysLT2受体的表达，并使用双CysLT1/2受体拮抗剂ONO-6950、CysLT1受体拮抗剂孟鲁司特和CysLT2受体特异性拮抗剂BayCysLT2RA评估它们在抗原诱导的支气管收缩中的功能作用。
在5名非哮喘受试者中的5例以及2名哮喘受试者中的2例中，CysLT1受体表达于支气管平滑肌、上皮细胞和肺泡白细胞。另一方面，虽然5名非哮喘受试者中CysLT2受体的表达程度各不相同，但在2名哮喘受试者中的2例中，哮喘肺组织中支气管平滑肌、上皮细胞和肺泡白细胞均检测到CysLT2受体表达。在非哮喘标本中，即使先用CysLT1受体特异性拮抗剂孟鲁司特预处理，CysLT2受体拮抗剂也不影响抗原诱导的支气管收缩。然而，在2名哮喘受试者之一分离的支气管中，CysLT2受体拮抗剂可抑制收缩，CysLT1和CysLT2受体的双重拮抗作用对过敏反应性收缩产生相加抑制作用。
CysLT2受体在哮喘受试者分离的肺标本中表达。CysLT2受体的激活可能在某些哮喘人群中导致抗原诱导的支气管收缩。
