Title
Selective effects of carbamate pesticides on rat neuronal nicotinic acetylcholine receptors and rat brain acetylcholinesterase
Author
Prins Maurits Laboratorium TNO
Smulders, C.J.G.M.
Bueters, T.J.H.
van Kleef, R.G.D.M.
Vijverberg, H.P.M.
Publication year
2003
Abstract
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
Subject
Carbamate pesticides
Neuronal nicotinic acetylcholine receptor
Rat brain acetylcholinesterase
Two-microelectrode voltage clamp
Xenopus oocytes
IC 50
Xenopus laevis
Acetylcholinesterase
Animals
Brain
Carbamates
Cholinesterase Inhibitors
Dose-Response Relationship, Drug
Inhibitory Concentration 50
Insecticides
Male
Membrane Potentials
Neurons
Oocytes
Patch-Clamp Techniques
Protein Isoforms
Rats
Rats, Wistar
Receptors, Nicotinic
Structure-Activity Relationship
Xenopus laevis
Xenopus laevis
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DOI
https://doi.org/10.1016/j.taap.2003.07.011
TNO identifier
237426
ISSN
0041-008X
Source
Toxicology and Applied Pharmacology, 193 (193), 139-146
Document type
article