Quinidine is a competitive antagonist at alpha 1- and alpha 2-adrenergic receptors.
Quinidine is a competitive antagonist at alpha 1- and alpha 2-adrenergic receptors.
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奎尼丁是 α1 和 α2 肾上腺素受体的竞争性拮抗剂。
DOI：
10.1161/01.res.55.3.376
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发表时间：
1984
影响因子：
20.1
通讯作者：
Insel,PA
中科院分区：
文献类型：
--
作者：
Motulsky,HJ;Maisel,AS;Snavely,MD;Insel,PA
虽然奎尼丁已知在心血管系统中具有抗肾上腺素能作用，但其发挥这些作用的确切机制尚未明确。我们询问奎尼丁是否直接与肾上腺素能受体结合。放射性配体结合试验用于鉴定大鼠心脏和肾脏制备的膜上的α 1-肾上腺素能受体[（3 H）哌唑嗪结合位点）、人血小板和大鼠肾脏膜上的α 2-肾上腺素能受体[（3 H）育亨宾结合位点）以及大鼠心脏和肾脏膜上的β-肾上腺素能受体[（125 I）碘氰基吲哚酚结合位点）。尽管奎尼丁不能有效地竞争结合β-肾上腺素能受体，但它能竞争结合α 1-和α 2-肾上腺素能受体，并产生0.3-3 μ M的平衡解离常数。另外两种抗组胺药，利多卡因和普鲁卡因胺，没有竞争结合α-肾上腺素能受体。进一步的实验表明，奎尼丁与心脏α 1-和血小板α 2-肾上腺素能受体的相互作用是竞争性的和可逆的。我们的结论是，奎尼丁的抗肾上腺素能作用可以解释为占用和竞争性阻断α 1-和α 2-肾上腺素能受体。
Although quinidine is known to have antiadrenergic effects in the cardiovascular system, the precise mechanism by which it exerts these effects is not well defined. We asked whether quinidine binds directly to adrenergic receptors. Radioligand-binding assays were used to identify alpha 1-adrenergic receptors [( 3H]prazosin-binding sites) on membranes prepared from rat heart and kidney, alpha 2-adrenergic receptor [( 3H]yohimbine-binding sites) on human platelets and rat kidney membranes, and beta-adrenergic receptors [( 125I]iodocyanopindolol-binding sites) on rat heart and kidney membranes. Although it did not effectively compete for binding to beta-adrenergic receptors, quinidine competed for binding to alpha 1- and alpha 2-adrenergic receptors and yielded equilibrium dissociation constants of 0.3-3 microM. Two other antiarrhythmic agents, lidocaine and procainamide, did not compete for binding to alpha-adrenergic receptors. Further experiments demonstrated that the interactions of quinidine with the cardiac alpha 1- and platelet alpha 2-adrenergic receptors were competitive and reversible. We conclude that that antiadrenergic actions of quinidine can be explained by occupancy and competitive blockade of alpha 1- and alpha 2-adrenergic receptors.