Certain beta-blockers can decrease beta-adrenergic receptor number: I. Acute reduction in receptor number by tertatolol and bopindolol.
Certain beta-blockers can decrease beta-adrenergic receptor number: I. Acute reduction in receptor number by tertatolol and bopindolol.
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某些 β 受体阻滞剂可以减少 β 肾上腺素能受体数量： I. 特他洛尔和波吲洛尔可急性减少受体数量。
DOI：
10.1161/01.res.63.2.273
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发表时间：
1988
影响因子：
20.1
通讯作者：
O. Marasco
中科院分区：
文献类型：
--
作者：
A. de Blasi;M. Fratelli;O. Marasco
我们以前曾报道过一种有效的新型β受体阻滞剂，特他洛尔，当以治疗剂量给予健康志愿者时，可迅速减少人类单核白细胞β受体的数量。本研究探讨了β -拮抗剂与靶细胞体外培养对受体的调控机制。使用两种不同的细胞类型（人类单核白细胞和S49小鼠淋巴瘤细胞），并使用亲水性配体3H-CGP 12177（特异性表面受体）或亲脂性125I-pindolol（测量总受体）测量β -肾上腺素能受体。在β受体阻滞剂之间的比较中，特他洛尔和bopindolol，而不是心得安和品多洛尔，被发现能迅速（37摄氏度下1小时）减少β肾上腺素能受体的数量。这与异丙肾上腺素刺激的循环AMP积累的减少是平行的。无论测量表面受体还是总受体，受体的减少都是相同的；因此，这不是由于受体的隔离。这种效应不是由部分激动剂活性引起的（bopindolol是一种弱的部分激动剂）；在平行实验中，tertatolol和bopindolol，但不是pindolol（强效部分激动剂）和异丙肾上腺素（完全激动剂），减少β -肾上腺素能受体。最后，这种作用不是由于不可逆结合：不可逆阻滞剂溴-乙酰-阿普萘洛尔-甲烷（BAAM）诱导的受体还原在几个小时内是稳定的，而特他洛尔和博品多洛尔的作用在相同的时间内缓慢逆转。我们认为特他特洛尔和bopindolol对β -肾上腺素能受体有两种作用：它们竞争性地结合，然后它们修饰受体，使它们不再可与配体或儿茶酚胺结合。（摘要删节250字）
We have previously reported that a potent new beta-blocker, tertatolol, when given at therapeutic doses to healthy volunteers, rapidly reduced the number of human mononuclear leukocyte beta-receptors. In the present study, the mechanism of receptor regulation by beta-antagonists incubated with target cells in vitro was investigated. Two different cell types (human mononuclear leukocytes and S49 murine lymphoma cells) were used, and beta-adrenergic receptors were measured using either the hydrophilic ligand 3H-CGP 12177 (specific for surface receptors) or lipophilic 125I-pindolol (which measures total receptors). In a comparison between beta-blockers, tertatolol and bopindolol, but not propranolol and pindolol, were found to rapidly (1 hour at 37 degrees C) reduce the number of beta-adrenergic receptors. This was paralleled by a reduction in isoproterenol-stimulated cyclic AMP accumulation. The reduction in receptors was the same whether surface or total receptors were measured; thus, it was not due to receptor sequestration. This effect was not caused by partial agonist activity (bopindolol is a weak partial agonist); in parallel experiments, tertatolol and bopindolol, but not pindolol (potent partial agonist) and isoproterenol (full agonist), reduced beta-adrenergic receptors. Finally, this effect was not due to irreversible binding: the receptor reduction induced by the irreversible blocker bromo-acetyl-alprenolol-methane (BAAM) was stable for several hours, while the effect of tertatolol and bopindolol was slowly reversed over the same time course. We suggest that tertatolol and bopindolol have two effects on beta-adrenergic receptors: they bind competitively, and then they modify the receptors so that they are no longer available for binding by ligands or catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)
非典型激动剂对 β1 和 β2 肾上腺素能受体的选择性调节。
DOI：
--
发表时间：
1985
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Neve,KA;Barrett,DA;Molinoff,PB
通讯作者：
Molinoff,PB
激动剂和拮抗剂与β肾上腺素能受体相互作用的动力学分析。
DOI：
--
发表时间：
1986
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Contreras,ML;Wolfe,BB;Molinoff,PB
通讯作者：
Molinoff,PB