Characterization of high-affinity beta2-adrenergic receptor binding of (-)-[3H]-dihydroalprenolol to human polymorphonuclear cell particulates.
Characterization of high-affinity beta2-adrenergic receptor binding of (-)-[3H]-dihydroalprenolol to human polymorphonuclear cell particulates.
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(-)-[3H]-二氢阿普洛尔与人多形核细胞颗粒的高亲和力 β2-肾上腺素受体结合的表征。
DOI：
10.5555/uri:pii:0022214378901130
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发表时间：
1978
期刊：
影响因子：
--
通讯作者：
P. Insel
中科院分区：
文献类型：
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作者：
S. Galant;S. Galant;S. Underwood;S. Underwood;L. Duriseti;L. Duriseti;P. Insel;P. Insel
人中性粒细胞对β-肾上腺素能儿茶酚胺有很好的反应，包括升高细胞内环AMP水平和抑制溶酶体内容物的释放。在直接配体结合研究中使用放射性β-肾上腺素能拮抗剂（-）-[3 H]DHA，我们已经确定并表征了中性粒细胞颗粒制剂上的β-肾上腺素能受体。这些颗粒快速（t1/2小于1 min）和可逆（t1/2 = 8 - 9 min）结合DHA。DHA结合是可饱和的，具有高亲和力（解离常数= 1至5 nM）和低容量（870 +/- 128受体/细胞，平均值+/- S.D.）一种单一的结合位点β-肾上腺素能激动剂和拮抗剂对DHA结合位点的竞争具有立体选择性[（-）-异构体比（+）-异构体更有效]。在此类竞争研究中，肾上腺素能药物效力的等级顺序表明这些受体为β 2型。由于中性粒细胞可以获得高纯度，相对容易，在中性粒细胞的药理学和配体结合研究的结合使用提供了一个有用的系统，研究β-肾上腺素能受体和它们的功能，在人类受试者。
Human PMNs have well-described responses to beta-adrenergic catecholamines; these include elevation of cellular levels of cyclic AMP and inhibition of the release of lysosomal contents. Using the radioactive beta-adrenergic antagonist (-)-[3H]DHA in direct ligand-binding studies, we have identified and characterized beta-adrenergic receptors on particulate preparations of PMNs. These particulates bind DHA rapidly (t1/2 less than 1 min) and reversibly (t1/2 = 8 to 9 min). DHA binding is saturable and of high affinity (dissociation constant = 1 to 5 nM) and low capacity (870 +/- 128 receptors/cell, mean +/- S.D.) to a single class of binding sites. Competition for DHA binding sites by both beta-adrenergic agonists and antagonists is stereoselective [(-)-isomers more potent that (+)-isomers]. The rank order of potency of adrenergic agents in such competition studies indicates that these receptors are of the beta2 type. Since PMNs can be obtained in high purity with relative ease, the combined use of pharmacologic and ligand-binding studies in PMNs provide a useful system for studying beta-adrenergic receptors and their function in human subjects.