Isoproterenol antagonizes endothelial permeability induced by thrombin and thrombin receptor peptide.
Isoproterenol antagonizes endothelial permeability induced by thrombin and thrombin receptor peptide.
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DOI：
10.1152/jappl.1993.75.3.1171
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发表时间：
1993-09
影响因子：
3.3
通讯作者：
F. Minnear;M. Demichele;S. Leonhardt;T. Andersen;M. Teitler
中科院分区：
文献类型：
--
作者：
F. Minnear;M. Demichele;S. Leonhardt;T. Andersen;M. Teitler
我们确定了1）凝血酶受体的氨基末端肽增加内皮渗透性的程度是否与α-凝血酶相当，2）异丙肾上腺素是否通过对凝血酶的拮抗作用或通过降低基线渗透性来减弱凝血酶诱导的内皮渗透性增加，3）异丙肾上腺素是否通过刺激β 2-肾上腺素能受体来降低渗透性。通过125 I标记的白蛋白的清除率来评估牛肺动脉内皮细胞（CCL 209）单层的渗透性。凝血酶受体肽在1 μ M时增加渗透性，但需要10至100 μ M的剂量才能等于1 μ M α-凝血酶的渗透性反应。剂量反应实验表明，异丙肾上腺素拮抗α-凝血酶和凝血酶受体肽对内皮细胞通透性的作用，并降低基线通透性。异丙肾上腺素的这种渗透性降低作用通过刺激β 2-肾上腺素能受体而发生。部分β 2-激动剂特布他林可阻止凝血酶诱导的通透性，而部分β 1-激动剂多巴酚丁胺则不能。特布他林的活性立体异构体和外消旋形式模仿异丙肾上腺素的作用，但非活性立体异构体没有影响。特异性β 2受体拮抗剂ICI-118，551可阻止异丙肾上腺素的渗透性降低作用，而特异性β 1受体拮抗剂ICI-89，406则不能。125 I-吲哚洛尔与ICI-118，551或ICI-89，406的竞争性结合研究表明，细胞膜匀浆上存在β-肾上腺素能受体，主要是β 2-受体。（250字处删节）
We determined whether 1) amino-terminal peptides of the thrombin receptor increase endothelial permeability to a comparable extent as alpha-thrombin does, 2) isoproterenol attenuates the thrombin-induced increase in endothelial permeability by an antagonistic action to that of thrombin or by lowering baseline permeability, and 3) isoproterenol decreases permeability via stimulation of the beta 2-adrenergic receptor. Permeability across monolayers of bovine pulmonary artery endothelial cells (CCL 209) was assessed by the clearance of 125I-labeled albumin. Thrombin receptor peptides increased permeability at 1 microM but required a dose of between 10 and 100 microM to equal the permeability response of 1 microM alpha-thrombin. Dose-response experiments demonstrated that isoproterenol antagonized the action of alpha-thrombin and a thrombin receptor peptide on endothelial permeability and that it lowered baseline permeability. This permeability-decreasing action of isoproterenol occurred via stimulation of the beta 2-adrenergic receptor. Terbutaline, a partial beta 2-agonist, prevented the thrombin-induced permeability, but dobutamine, a partial beta 1-agonist, did not. The active stereoisomer of terbutaline and the racemic form mimicked the action of isoproterenol, but the inactive stereoisomer had no effect. ICI-118,551, a specific beta 2-receptor antagonist, prevented the permeability-decreasing action of isoproterenol, whereas ICI-89,406, a specific beta 1-receptor antagonist, did not. Competitive binding studies of 125I-pindolol with ICI-118,551 or ICI-89,406 demonstrated the presence of beta-adrenergic receptors, predominantly beta 2-receptors, on cell membrane homogenates.(ABSTRACT TRUNCATED AT 250 WORDS)