Winek R, Bhalla R
Eur J Pharmacol. 1982 Jan 22;77(2-3):89-94. doi: 10.1016/0014-2999(82)90001-2.
The beta-adrenergic antagonist, [3H]dihydroalprenolol, was used to label binding sites in crude rat myocardial plasma membranes. The specificity of binding was dependent on the temperature of the assay. Specific binding at 22 and 37 degree C and at concentrations of radioligand less than 5 nM was consistent with binding to the myocardial beta-receptor. Binding sites labeled at 4 degree C possessed quite different properties. Binding was non-stereoselective and of lower affinity. Agonist compounds were much less effective at competing for the labeled myocardial sites at 4 degree C than at 22 degree C. Those beta-antagonists which additionally possess pharmacological "quinidine-like' activity (e.g. propranolol, alprenolol) were potent competitors at 4 degree C, but competition was non-stereoselective. In contrast atenolol, a beta-antagonist devoid of "quinidine-like' activity was ineffective at 4 degree C. Furthermore, procaine, and quinidine itself were potent competitors of [3H]dihydroalprenolol binding at 4 degree C. Thus the specificity of [3H]dihydroalprenolol binding to rat heart membranes at 4 degree C appears to be directed non-stereoselectively at that portion of the competing molecule which recognized "quinidine-like' as opposed to adrenergic activity.
β - 肾上腺素能拮抗剂[³H]二氢烯丙洛尔被用于标记大鼠心肌粗制质膜中的结合位点。结合的特异性取决于测定温度。在22℃和37℃以及放射性配体浓度低于5 nM时的特异性结合与心肌β受体的结合一致。在4℃标记的结合位点具有截然不同的特性。结合是非立体选择性的且亲和力较低。激动剂化合物在4℃时竞争标记心肌位点的效果远不如在22℃时。那些还具有药理学“奎尼丁样”活性的β拮抗剂（如普萘洛尔、烯丙洛尔）在4℃时是有效的竞争者，但竞争是非立体选择性的。相比之下，没有“奎尼丁样”活性的β拮抗剂阿替洛尔在4℃时无效。此外，普鲁卡因和奎尼丁本身在4℃时是[³H]二氢烯丙洛尔结合的有效竞争者。因此，[³H]二氢烯丙洛尔在4℃时与大鼠心脏膜结合的特异性似乎非立体选择性地针对竞争分子中识别“奎尼丁样”而非肾上腺素能活性的部分。
