Subunit-dependent action of lead on neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes.
1. 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.
Oortgiesen
M
M
Research Institute of Toxicology, Utrecht University, The Netherlands.
Zwart
R
R
van Kleef
R G
RG
Vijverberg
H P
HP
D000818:Animals; D018076:DNA, Complementary / Q000235:genetics; D004594:Electrophysiology; D005786:Gene Expression Regulation / Q000187:drug effects; D007854:Lead / Q000633:toxicity*; D009865:Oocytes / Q000166:cytology / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis
D018076:DNA, Complementary; D011978:Receptors, Nicotinic; D007854:Lead