Effects of triethyl lead on various cholinergic parameters in the rat brain in vitro.
The effects of triethyl lead acetate (triethyl Pb) on the cholinergic system in the brain of the rats were investigated in vitro. Triethyl Pb, at concentrations below 10(-4) M, inhibited the depolarized release of acetylcholine (ACh) from slices of cortex and they synthesis of ACh in such slices, while it potentiated in a dose-dependent manner the non-depolarized release of ACh. In contrast, lead inhibited noncompetitively the high-affinity uptake of choline into synaptosomes with a Ki of 4.03 X 10(-6) M and the activity of choline acetyltransferase with a Ki of 4.07 X 10(-5) M. Triethyl Pb has an inhibitory effect (IC50 not equal to 5 X 10(-5) M) on the binding of [3H]quinuclidinyl benzilate to muscarinic ACh receptors. Triethyl Pb inhibited acetylcholinesterase activity slightly at 5 X 10(-5) and 10(-4) M. It is suggested that ACh transmission, in particular the synthesis of ACh and the release of ACh, is susceptible to organolead neurotoxicity.
Hoshi
F
F
Department of Veterinary Internal Medicine, School of Veterinary Medicine and Animal Sciences, Kitasato University, Aomori, Japan.
Kobayashi
H
H
Yuyama
A
A
Matsusaka
N
N
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D066298:In Vitro Techniques; D007854:Lead / Q000494:pharmacology*; D008297:Male; D009942:Organometallic Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D009942:Organometallic Compounds; D011976:Receptors, Muscarinic; D007854:Lead; C010360:triethyllead; D002795:Choline O-Acetyltransferase; D002794:Choline; D000109:Acetylcholine