Plotek Y, Atlas D
Eur J Biochem. 1983 Jul 1;133(3):539-44. doi: 10.1111/j.1432-1033.1983.tb07497.x.
An irreversible alpha-adrenergic blocker, benextramine [N,N'-bis(o-methoxybenzylamine-n-hexyl)-cysteamine] was used as a probe to study the possible interrelationship between alpha-adrenoceptors and the K+-activated Ca2+-channels. Benextramine, a tetraamine disulfide, acts irreversibly both on the alpha 1-adrenoceptor (t 1/2 = 3 min) and the alpha 2-adrenoceptors. These studies were carried out on rat brain synaptosomes, [3H]prazosin and [3H]clonidine binding. Benextramine blocked Ca2+ influx in rat brain synaptosomes under both depolarizing (75 mM KCl) and normal conditions (5 mM KCl). Its action at the channel is reversible with IC50 = 10 +/- 5 microM of the net Ca2+ influx. This makes benextramine a most potent Ca2+ blocker compared to verapamil or nicardipine (IC50 = 200 microM and 170 microM, respectively). Pretreatment of rat brain slices with benextramine gave a synaptosomal preparation which was devoid of either alpha 1-adrenergic or alpha 2-adrenergic binding capacity due to the irreversible binding of benextramine, but with an undisturbed Ca2+ influx. Thus, these results suggest that the alpha-adrenoceptors and the Ca2+-channels are independent of each other, and that full occupancy of the alpha-receptors does not affect the net calcium flux.
一种不可逆的α-肾上腺素能阻滞剂——苄环烷胺[N,N'-双(邻甲氧基苄胺-n-己基)-半胱胺]被用作探针，以研究α-肾上腺素能受体与钾离子激活的钙离子通道之间可能存在的相互关系。苄环烷胺是一种四胺二硫化物，对α1-肾上腺素能受体（半衰期=3分钟）和α2-肾上腺素能受体均有不可逆作用。这些研究是在大鼠脑突触体上进行的，采用[3H]哌唑嗪和[3H]可乐定结合法。在去极化（75 mM氯化钾）和正常条件（5 mM氯化钾）下，苄环烷胺均可阻断大鼠脑突触体中的钙离子内流。其对通道的作用是可逆的，净钙离子内流的IC50 = 10±5微摩尔。与维拉帕米或尼卡地平（IC50分别为200微摩尔和170微摩尔）相比，这使得苄环烷胺成为一种非常有效的钙离子阻滞剂。用苄环烷胺预处理大鼠脑片后得到的突触体制剂，由于苄环烷胺的不可逆结合，缺乏α1-肾上腺素能或α2-肾上腺素能结合能力，但钙离子内流不受影响。因此，这些结果表明α-肾上腺素能受体和钙离子通道相互独立，α-受体的完全占据不会影响净钙通量。
