Multiple binding sites for phencyclidine on the nicotinic acetylcholine receptor from Torpedo ocellata electric organ.
Multiple binding sites for phencyclidine on the nicotinic acetylcholine receptor from Torpedo ocellata electric organ.
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苯环己哌啶在来自鱼雷鱼电器官的烟碱乙酰胆碱受体上的多个结合位点。
DOI：
10.1016/0024-3205(84)90018-3
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发表时间：
1984
期刊：
影响因子：
6.1
通讯作者：
Y. Kloog
中科院分区：
文献类型：
--
作者：
R. Haring;Y. Kloog
本文研究了[3 H]-苯环己哌啶（[3 H]-PCP）与电鳐电器官乙酰胆碱受体富集膜在1 ~ 200 μM浓度范围内的结合。结果表明，[3 H]-PCP与两类位点结合：高亲和力（Kd= 6-9 μM）和低亲和力（Kd= 85 μM）结合位点。在无胆碱能药物存在下，[3 H]-PCP与~（125）I-α-银环蛇毒素（α-Bgt）的高亲和力结合位点与~（125）I-α-Bgt的结合位点之比为0.37，而低亲和力结合位点与~（125）I-α-Bgt的结合位点之比为1.06。α-银环蛇毒素（α-Bgt）、氨甲酰胆碱和d-筒箭毒碱可完全抑制低亲和力[3 H]-PCP结合。这种抑制作用以及与125 I-α-Bgt的1：1化学计量比表明，[3 H]-PCP以低亲和力结合的位点是乙酰胆碱（AcCho）结合位点。在1 μM α-Bgt阻断[~ 3 H]-PCP与AcCho结合位点结合的情况下，高亲和力[~ 3 H]-PCP位点与~（125）I-α-Bgt位点的比值为0.5，表明每个受体分子中存在一个高亲和力PCP位点。降低[3 H]-PCP对AcCho受体的表观亲和力以及丁卡因或地布卡因抑制[3 H]-PCP与该受体结合的效力。在后一种情况下，效应涉及从双相到简单抑制曲线的变化。结果表明，AcCho受体的非竞争性阻滞剂也可能影响其自身的位点，并且它们也通过结合AcCho结合位点来实现这一目的。这也可以从浓度为10− 3至10− 4 M的未标记五氯苯酚加速[3 H]-五氯苯酚从其高亲和力结合位点解离推断出来，此时药物也占据AcCho结合位点。
Abstract Binding of [3 H]-phencyclidine ([3 H]-PCP) to acetylcholine-receptor enriched membrane from Torpedo ocellata electric organ was studied over a ligand concentration range of 1 to 200 μM. The results indicate that [3 H]-PCP is boud to two classes of sites: high affinity (Kd= 6–9 μM) and low affinity (Kd= 85 μM) binding sites. In the absence of cholinergic drugs the ratio of high affinity [3 H]-PCP binding sites to 125 I-α-bungarotoxin (α-Bgt) binding sites is 0.37, and that of low affinity [3 H]-PCP binding sites to 125 I-α-Bgt is 1.06. Low affinity [3 H]-PCP binding can be completely inhibited by α-bungarotoxin (α-Bgt), carbamylcholine and d-tubocurarine. This inhibition, together with the one to one stoichiometry with 125 I-α-Bgt, suggests that the sites to which [3 H]-PCP binds with low affinity are the acetylcholine (AcCho) binding sites. In the presence of 1 μM α-Bgt which blocks binding of [3 H]-PCP to the AcCho binding sites, the ratio of high affinity [3 H]-PCP sites to 125 I-α-Bgt sites is 0.5, indicating the existence of one high affinity PCP site per receptor molecule, The toxin, however, decreases the apparent affinity of [3 H]-PCP towards the AcCho receptor as well as the potency of tetracaine or dibucaine in inhibiting [3 H]-PCP binding to that receptor. In the latter case the effect involves changes from a biphasic to a simple inhibition curve. The results suggest that non-competitive blockers to the AcCho receptors may affect their own sites as well, and that they do this also by binding to the AcCho binding sites. This is also inferred from the accelerated dissociation of [3 H]-PCP from its high affinity binding sites by unlabeled PCP in the concentration range of 10− 3 to 10− 4 M, at which the drug occupies AcCho binding sites as well.
可逆拮抗剂占据与乙酰胆碱受体功能之间的关系。
DOI：
--
发表时间：
1981
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Sine,SM;Taylor,P
通讯作者：
Taylor,P