铅对非洲爪蟾卵母细胞中表达的神经元烟碱型乙酰胆碱受体的亚基依赖性作用。

Subunit-dependent action of lead on neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes.

Oortgiesen M, Zwart R, van Kleef R G, Vijverberg H P

Research Institute of Toxicology, Utrecht University, The Netherlands.

Clin Exp Pharmacol Physiol. 1995 May;22(5):364-5. doi: 10.1111/j.1440-1681.1995.tb02018.x.

Abstract

Pb2+ affects neuronal nicotinic acetylcholine receptors (nAChR) in N1E-115 neuroblastoma cells in a dual manner. At nanomolar concentrations a blockade is observed, while at submillimolar concentrations this blocking effect is reversed. 2. The Xenopus oocyte expression system was used to examine whether the dual effect of Pb2+ is related to a differential action on nAChR subtypes. Effects of Pb2+ were investigated in oocytes expressing nAChR after co-injection of alpha 3 and beta 2 or alpha 3 and beta 4 cDNA. 3. At 1-250 mumol/L, Pb2+ causes a 10-1000% increase of the response mediated by the alpha 3 beta 2 nAChR. 4. Pb2+ blocks ACh-induced inward currents mediated by alpha 3 beta 4 nAChR. The inhibitory potency of Pb2+ greatly varies between cells. In 50% of the cells concentrations < or = 1 mumol/L Pb2+ blocked the nicotinic response by 31-93%. In the other cells even at higher concentrations Pb2+ caused only 0-65% inhibition. 5. These results show that Pb2+ may both potentiate and block nAChR, depending on the type of nAChR subunit expressed.

摘要

铅离子（Pb2+）对N1E - 115神经母细胞瘤细胞中的神经元烟碱型乙酰胆碱受体（nAChR）具有双重影响。在纳摩尔浓度下可观察到阻断作用，而在亚毫摩尔浓度下这种阻断作用会逆转。2. 非洲爪蟾卵母细胞表达系统被用于研究Pb2+的双重效应是否与对nAChR亚型的差异作用有关。在共注射α3和β2或α3和β4互补DNA后，研究了Pb2+对表达nAChR的卵母细胞的影响。3. 在1 - 250μmol/L浓度下，Pb2+使由α3β2 nAChR介导的反应增加10 - 1000%。4. Pb2+阻断由α3β4 nAChR介导的乙酰胆碱（ACh）诱导的内向电流。Pb2+的抑制效力在不同细胞间差异很大。在50%的细胞中，浓度≤1μmol/L的Pb2+使烟碱反应阻断31 - 93%。在其他细胞中，即使在更高浓度下，Pb2+也仅引起0 - 65%的抑制。5. 这些结果表明，Pb2+可能根据所表达的nAChR亚基类型增强或阻断nAChR。