Effects of arsenic on cholinergic parameters in brain in vitro.
The effects of sodium arsenite (arsenite) on the cholinergic system in the brain of the mouse were investigated in vitro and compared with those of N-ethylmaleimide (NEM) and iodoacetate, both of which are alkylating sulfhydryl reagents. Arsenite, at concentrations greater than 10(-4) M, inhibited depolarized and nondepolarized release of acetylcholine (ACh) from cerebral slices, the synthesis of ACh in the slices, high-affinity uptake of choline into synaptosomes and activity of acetylcholinesterase (AChE). On the other hand, arsenite potentiated dose-dependently the activity of choline acetyltransferase (ChAT). N-Ethylmaleimide and iodoacetate showed inhibitory effects similar to those of arsenite. However, some exceptions were that N-ethylmaleimide did not have any effect on the nondepolarized release of ACh while iodoacetate had no effect on high affinity uptake of choline and activity of AChE. In contrast to arsenite, N-ethylmaleimide and iodoacetate inhibited the activity of ChAT. Neither of arsenite, N-ethylmaleimide nor iodoacetate showed any effect on the binding of [3H]quinuclidinyl benzilate to muscarinic ACh receptors. Although arsenite is thought to inhibit the cholinergic system in brain in vivo, its potentiating effect on ChAT and inhibition of AChE may reduce this harmful effect.
Department of Veterinary Medicine, Faculty of Agriculture, Iwate University, Morioka, Japan.
H
H
Kobayashi
A
A
Yuyama
M
M
Ishihara
N
N
Matsusaka
D000109:Acetylcholine / Q000096:biosynthesis; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001151:Arsenic / Q000494:pharmacology / Q000633:toxicity*; D018053:Arsenites; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects
D018053:Arsenites; D009419:Nerve Tissue Proteins; D011950:Receptors, Cholinergic; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; C015001:arsenite; D001151:Arsenic; D002794:Choline; D000109:Acetylcholine; D005033:Ethylmaleimide