Competitive interaction of gallamine with multiple muscarinic receptors.
Competitive interaction of gallamine with multiple muscarinic receptors.
复制标题
没食子胺与多种毒蕈碱受体的竞争性相互作用。
DOI：
10.1016/0006-2952(82)90477-4
复制
发表时间：
1982
影响因子：
5.8
通讯作者：
W. Hoss
中科院分区：
文献类型：
--
作者：
J. Ellis;W. Hoss
加拉胺是一种位于(尼古丁)神经肌肉接头的胆碱能拮抗剂，在几个系统中具有抗肌肉碱的效力。本文报道了在大鼠的脑干和前脑中，加拉胺以竞争性的方式抑制[~3H]奎宁基苯甲酸酯(QNB)的结合。由这些研究得出的占位曲线表明，加拉胺对不同亚群的M受体具有很大不同的亲和力，这一发现使加拉胺有别于经典的M受体拮抗剂，如阿托品和QNB。对加拉胺的亲和力差异最大的是脑干，数据可以令人满意地符合双部位模型，77%的受体具有高亲和力(Kd=25 NM)，23%的受体具有低亲和力(93μM)。此外，这些亲和力与卡巴胆碱(一种激动剂)的亲和力显示出等级顺序相关，尽管到目前为止，加拉胺还没有表现出激动剂(或部分激动剂)的活性。拮抗剂和激动剂都能对M受体表现出多种亲和力，这一发现表明，这些受体的亚群之间存在着根本的差异。
Gallamine, a cholinergic antagonist at the (nicotinic) neuromuscular junction, possesses antimuscarinic potency in several systems. We report here that gallamine inhibited the binding of [3H]quinuclidinyl benzilate (QNB) in a competitive manner in the brainstem and forebrain of the rat. The occupancy curves derived from these studies suggest that gallamine has widely varying affinities for different subpopulations of muscarinic receptors, a finding which sets gallamine apart from classical muscarinic antagonists such as atropine and QNB. The greatest difference in affinities for gallamine occurred in the brainstem, where the data could be satisfactorily fitted to a two-site model, with 77% of the receptors having high affinity (Kd= 25 nM) and 23% low affinity (93 μM). Further, these affinities displayed rank order correlation with those of carbachol (an agonist), although gallamine has not, so far, displayed agonist (or partial agonist) activity. The finding that antagonists as well as agonists can display multiple affinities for muscarinic receptors suggests that there are fundamental differences among subpopulations of these receptors.