Selective effects of carbamate pesticides on rat neuronal nicotinic acetylcholine receptors and rat brain acetylcholinesterase
article
Effects of commonly used carbamate pesticides on rat neuronal nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes have been investigated using the two-electrode voltage clamp technique. The potencies of these effects have been compared to the potencies of the carbamates to inhibit rat brain acetylcholinesterase. The potency order of six carbamates to inhibit α4β4 nicotinic receptors is fenoxycarb > EPTC > carbaryl, bendiocarb > propoxur > aldicarb with IC50 values ranging from 3 μM for fenoxycarb to 165 μM for propoxur and >1 mM for aldicarb. Conversely, the potency order of these carbamates to inhibit rat brain acetylcholinesterase is bendiocarb > propoxur, aldicarb > carbaryl ≫ EPTC, fenoxycarb with IC50 values ranging from 1 μM for bendiocarb to 17 μM for carbaryl and ≫1 mM for EPTC and fenoxycarb. The α4β2, α3β4, and α3β2 nicotinic acetylcholine receptors are inhibited by fenoxycarb, EPTC, and carbaryl with potency orders similar to that for α4β4 receptors. Comparing the potencies of inhibition of the distinct subtypes of nicotinic acetylcholine receptors shows that the α3β2 receptor is less sensitive to inhibition by fenoxycarb and EPTC. The potency of inhibition depends on the carbamate as well as on a combination of α and β subunit properties. It is concluded that carbamate pesticides affect different subtypes of neuronal nicotinic receptors independently of acetylcholinesterase inhibition. This implicates that neuronal nicotinic receptors are additional targets for some carbamate pesticides and that these receptors may contribute to carbamate pesticide toxicology, especially after long-term exposure. © 2003 Elsevier Inc. All rights reserved.
Chemicals/CAS: acetylcholinesterase, 9000-81-1; aldicarb, 116-06-3; bendiocarb, 22781-23-3; carbaril, 63-25-2; fenoxycarb, 72490-01-8; propoxur, 114-26-1; Acetylcholinesterase, EC 3.1.1.7; Carbamates; Cholinesterase Inhibitors; Insecticides; Protein Isoforms; Receptors, Nicotinic
Chemicals/CAS: acetylcholinesterase, 9000-81-1; aldicarb, 116-06-3; bendiocarb, 22781-23-3; carbaril, 63-25-2; fenoxycarb, 72490-01-8; propoxur, 114-26-1; Acetylcholinesterase, EC 3.1.1.7; Carbamates; Cholinesterase Inhibitors; Insecticides; Protein Isoforms; Receptors, Nicotinic
Topics
Carbamate pesticidesNeuronal nicotinic acetylcholine receptorRat brain acetylcholinesteraseTwo-microelectrode voltage clampXenopus oocytesIC 50Xenopus laevisAcetylcholinesteraseAnimalsBrainCarbamatesCholinesterase InhibitorsDose-Response Relationship, DrugInhibitory Concentration 50InsecticidesMaleMembrane PotentialsNeuronsOocytesPatch-Clamp TechniquesProtein IsoformsRatsRats, WistarReceptors, NicotinicStructure-Activity RelationshipXenopus laevisXenopus laevis
TNO Identifier
237426
ISSN
0041008X
Source
Toxicology and Applied Pharmacology, 193(2), pp. 139-146.
Pages
139-146
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