Selective alpha-2 adrenoceptor blockade by SK&F 86466: in vitro characterization of receptor selectivity.
Selective alpha-2 adrenoceptor blockade by SK&F 86466: in vitro characterization of receptor selectivity.
复制标题
SK 选择性 α-2 肾上腺素受体阻断剂
DOI：
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发表时间：
1986
影响因子：
3.5
通讯作者：
W. D. Matthews
中科院分区：
文献类型：
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作者：
J. Hieble;R. Demarinis;P. J. Fowler;W. D. Matthews
SK&F 86466（6-氯- n -甲基-2,3,4,5-四氢-1- h -3-benzazepine）是一种有效的选择性α -2肾上腺素受体拮抗剂。在豚鼠心房（受体解离常数(KB) = 13-17 nM）中，可通过阻断克拉定或B-HT 920介导的α -2肾上腺素介导的神经抑制作用，或通过增强预先标记的豚鼠心房、狗脾动脉或兔耳动脉神经诱发的[3H]去甲肾上腺素的释放来证明突触前α -2肾上腺素的拮抗作用。B-HT 920作为犬大隐静脉的收缩剂，其浓度-反应曲线平行向右移动，可见交界后α -2肾上腺素能受体阻滞。该测试系统中SK&F 86466的KB为42 nM。SK&F 86466对α -1肾上腺素受体的亲和力要低得多，对兔耳动脉去甲肾上腺素介导的收缩的KB为900 nM，对犬隐静脉SK&F 89748诱导的收缩的KB为1100 nM。SK&F 86466的α -2/ α -1肾上腺素受体选择性比与育亨宾等药物相当，使SK&F 86466成为表征α -2肾上腺素受体及其生理作用研究的有用工具。
SK&F 86466 (6-chloro-N-methyl-2,3,4,5-tetrahydro-1-H-3-benzazepine) is a potent and selective antagonist at alpha-2 adrenoceptors. Prejunctional alpha-2 adrenoceptor antagonism can be demonstrated either by blockade of the alpha-2 adrenoceptor-mediated neuroinhibitory effect of clonidine or B-HT 920 in the guinea-pig atrium [receptor dissociation constant (KB) = 13-17 nM] or by potentiation of nerve-evoked release of [3H]norepinephrine from prelabeled guinea-pig atria, dog splenic artery or rabbit ear artery. Blockade of the postjunctional alpha-2 adrenoceptor was also seen, as demonstrated by a parallel shift to the right of the concentration-response curve for B-HT 920 as a constrictor agent in the dog saphenous vein. The KB for SK&F 86466 in this test system was 42 nM. The affinity of SK&F 86466 for the alpha-1 adrenoceptor is much lower, with a KB of 900 nM against norepinephrine-mediated constriction in the rabbit ear artery, or 1100 nM vs. SK&F 89748-induced constriction in the dog saphenous vein. The alpha-2/alpha-1 adrenoceptor selectivity ratio of SK&F 86466 is comparable to that obtained with agents such as yohimbine, making SK&F 86466 a useful tool for characterization of alpha-2 adrenoceptors and for investigation of their physiological role.