[环核苷酸磷酸二酯酶III/IV型抑制剂SDZ ISQ 844对人外周血白细胞组胺释放的影响]

[Effects of SDZ ISQ 844, a cyclic nucleotide phosphodiesterase isozyme type III/IV inhibitor, on the release of histamine from human peripheral leukocytes].

作者信息

Horikoshi S, Imai T, Okamoto M, Sugeta A, Idaira K, Adachi M

机构信息

First Department of Internal Medicine, School of Medicine, Showa University.

出版信息

Arerugi. 1997 May;46(5):426-32.

PMID:9232912

Abstract

We studied the effects of SDZ ISQ 844, a cyclic nucleotide phosphodiesterase (PDE) isozyme type III/IV inhibitor, and salbutamol on the release of histamine from activated human peripheral leukocytes. We stimulated the leukocyte suspensions with calcium ionophore A23187 (Ca-I, 10(-6 M) accompanied with SDZ ISQ 844 (10(-7) M, 10(-6) M, 10(-5) M), salbutamol (10(-7) M, 10(-6) M, 10(-5) M) and combination of SDZ ISQ 844 and salbutamol (10(-7) M, 10(-6) M, 10(-5) M), and measured the levels of histamine in the supernatant fluid and total cyclic AMP levels in the leukocyte suspensions. The increase of histamine levels induced by Ca-I was significantly inhibited by SDZ ISQ 844 (10(-6) M, 10(-5) M) in a dose-dependent manner (p < 0.05, p < 0.01). Salbutamol at the concentration until 10(-5) M did not inhibit the increase of histamine levels. Combination of SDZ ISQ 844 and salbutamol significantly inhibited the increase of histamine levels (10(-6) M, 10(-5) M) in a dose-dependent manner (p < 0.05, p < 0.01). The inhibition of the histamine release by SDZ ISQ 844 (10(-5) M was enhanced significantly by salbutamol (10(-5) M) (p < 0.05). Total cyclic AMP levels in the leukocytes suspensions increased significantly by SDZ ISQ 844 (10(-5) M) and combination of SDZ ISQ 844 and salbutamol (10(-6) M, 10(-5) M) in a dose-dependent manner (p < 0.05, p < 0.01). The increase of cyclic AMP levels by SDZ ISQ 844 (10(-5) M) was enhanced by salbutamol significantly (p < 0.01). These results suggest that selective inhibition of PDE isozyme type III/IV protects the release of histamine from human activated leukocytes in connection with intracellular cyclic AMP levels and the protection is enhanced by beta-agonist.

摘要

我们研究了环核苷酸磷酸二酯酶（PDE）III/IV型抑制剂SDZ ISQ 844和沙丁胺醇对激活的人外周血白细胞组胺释放的影响。我们用钙离子载体A23187（Ca-I，10⁻⁶ M）刺激白细胞悬液，同时加入SDZ ISQ 844（10⁻⁷ M、10⁻⁶ M、10⁻⁵ M）、沙丁胺醇（10⁻⁷ M、10⁻⁶ M、10⁻⁵ M）以及SDZ ISQ 844与沙丁胺醇的组合（10⁻⁷ M、10⁻⁶ M、10⁻⁵ M），并测量上清液中组胺水平以及白细胞悬液中总环磷酸腺苷（cAMP）水平。Ca-I诱导的组胺水平升高被SDZ ISQ 844（10⁻⁶ M、10⁻⁵ M）以剂量依赖方式显著抑制（p < 0.05，p < 0.01）。浓度达10⁻⁵ M的沙丁胺醇未抑制组胺水平的升高。SDZ ISQ 844与沙丁胺醇的组合以剂量依赖方式显著抑制组胺水平升高（10⁻⁶ M、10⁻⁵ M）（p < 0.05，p < 0.01）。SDZ ISQ 844（10⁻⁵ M）对组胺释放的抑制作用被沙丁胺醇（10⁻⁵ M）显著增强（p < 0.05）。SDZ ISQ 844（10⁻⁵ M）以及SDZ ISQ 844与沙丁胺醇的组合（10⁻⁶ M、10⁻⁵ M）使白细胞悬液中总cAMP水平以剂量依赖方式显著升高（p < 0.05，p < 0.01）。SDZ ISQ 844（10⁻⁵ M）使cAMP水平的升高被沙丁胺醇显著增强（p < 0.01）。这些结果表明，对PDE III/IV型同工酶的选择性抑制与细胞内环磷酸腺苷水平相关，可保护人激活白细胞释放组胺，且β-激动剂可增强这种保护作用。