Phencyclidine in nanomolar concentrations binds to synaptosomes and blocks certain potassium channels.
Phencyclidine in nanomolar concentrations binds to synaptosomes and blocks certain potassium channels.
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纳摩尔浓度的苯环利定与突触体结合并阻断某些钾通道。
DOI：
10.1073/pnas.80.12.3855
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发表时间：
1983
影响因子：
11.1
通讯作者：
Ickowicz,RK
中科院分区：
文献类型：
--
作者：
Blaustein,MP;Ickowicz,RK
苯环己哌啶[1-(苯基环己基)哌啶； [PCP]，低剂量（约等于 0.1-0.2 毫克/公斤体重）会诱发人类精神分裂症样行为综合征；这种效应归因于神经元 K 通道的阻断。我们使用 K 刺激的 86Rb 流出测定来证明低浓度的 PCP (10-50 nM) 会阻断大鼠大脑突触体中的一类去极化激活的 K 通道 - 夹断突触前神经末梢。剂量反应曲线是双相的，需要更高的 PCP 浓度（大于 10 µM）来阻止 K 刺激的 86Rb 流出的剩余部分。突触体的 [3H]PCP 结合曲线也是双相的：PCP 以高亲和力（Kd 约等于 6.0 X 10(-8) M）与某些组分结合，并以低得多的亲和力（Kd 约等于 1.15 X 10(4) M）与其他组分结合。五氯苯酚可以用紫外线光活化形成共价键：紫外线照射后，先前结合的[3H]五氯苯酚不再被大量过量的未标记五氯苯酚取代。 [3H]PCP 与突触体共价结合后的 NaDodSO4/聚丙烯酰胺凝胶电泳研究的初步数据表明，高亲和力结合位点可能位于大蛋白质上（Mr 约等于 220,000）。我们得出结论，高亲和力 PCP 结合蛋白与被纳摩尔浓度的 PCP 阻断的 K 通道相关。阻断这些通道可以通过延长突触前神经末梢的动作电位持续时间，增强钙的进入和神经递质的释放，从而改变参与行为表达的中央突触的传递。
Phencyclidine [1-(phenylcyclohexyl)piperidine; PCP], in low dose (approximately equal to 0.1-0.2 mg/kg of body weight), induces a schizophrenia-like behavioral syndrome in man; this effect has been attributed to block of neuronal K channels. We used a K-stimulated 86Rb efflux assay to demonstrate that low concentrations of PCP (10-50 nM) block a class of depolarization-activated K channels in rat brain synaptosomes--pinched-off presynaptic nerve terminals. The dose-response curve is biphasic, and much higher PCP concentrations (greater than 10 microM) are required to block the remainder of the K-stimulated 86Rb efflux. The [3H]PCP binding curve for synaptosomes is also biphasic: PCP binds to some components with high affinity (Kd approximately equal to 6.0 X 10(-8) M), and to other components with much lower affinity (Kd approximately equal to 1.15 X 10(4) M). PCP can be photoactivated with UV light to form covalent bonds: after UV irradiation, previously-bound [3H]PCP is no longer displaceable by a large excess of unlabeled PCP. Preliminary data from NaDodSO4/polyacrylamide gel electrophoresis studies after covalent binding of [3H]PCP to synaptosomes, suggest that the high-affinity binding site may be on a large protein (Mr approximately equal to 220,000). We conclude that the high-affinity PCP binding protein is associated with the K channels that are blocked by nanomolar concentrations of PCP. Block of these channels could, by prolonging action-potential duration in presynaptic nerve terminals, enhance calcium entry and neurotransmitter release, thereby altering transmission at central synapses involved in behavioral expression.