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


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



Clinical and Experimental Pharmacology and Physiology 22(5): 364-365



ISSN/ISBN: 0305-1870

PMID: 7554431

DOI: 10.1111/j.1440-1681.1995.tb02018.x

1. Pb-2+ 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 Pb-2+ is related to a differential action on nAChR subtypes. Effects of Pb-2+ 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 mu-mol/L, Pb-2+ causes a 10-1000% increase of the response mediated by the alpha-3-beta-2 nAChR. 4. Pb-2+ blocks ACh-induced inward currents mediated by alpha-3,beta-4 nAChR. The inhibitory potency of Pb-2+ greatly varies between cells. In 50% of the cells concentrations ltoreq 1 mu-mol/L Pb-2+ blocked the nicotinic response by 31-93%. In the other cells even at higher concentrations Pb-2+ caused only 0-65% inhibition. 5. These results show that Pb-2+ may both potentiate and block nAChR, depending on the type of nAChR subunit expressed.

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Accession: 009486355

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