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SUBUNIT‐DEPENDENT ACTION OF LEAD ON NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS EXPRESSED IN XENOPUS OOCYTES
Author(s) -
Oortgiesen Marga,
Zwart Ruud,
Kleef Regina G. D. M.,
Vijverberg Henk P. M.
Publication year - 1995
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1995.tb02018.x
Subject(s) - xenopus , acetylcholine receptor , nicotinic agonist , protein subunit , acetylcholine , receptor , microbiology and biotechnology , nicotinic acetylcholine receptor , neuroscience , chemistry , ganglion type nicotinic receptor , biology , pharmacology , biochemistry , gene
SUMMARY 1. Pb 2+ affects neuronal nicotinic acetylcholine receptors (nAChR) in NIE‐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 a3 and β2 or α3 and β4 cDNA. 3. At 1–250 μmol/L, Pb 2+ causes a 10–1000% increase of the response mediated by the α3β2 nAChR. 4. Pb 2+ blocks ACh‐induced inward currents mediated by α3β4 nAChR. The inhibitory potency of Pb 2+ greatly varies between cells. In 50% of the cells concentrations ≤μmol/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.