Brain regional acetylcholinesterase activity and muscarinic acetylcholine receptors in rats after repeated administration of cholinesterase inhibitors and its withdrawal.
Activity of acetylcholinesterase (AChE) and specific binding of [(3)H]quinuclidinyl benzilate (QNB), [(3)H]pirenzepine (PZP) and [(3)H]AF-DX 384 to muscarinic acetylcholine receptor (mAChR) preparations in the striatum, hippocampus and cortex of rats were determined 1, 6 and 11 days after the last treatment with an organophosphate DDVP, a carbamate propoxur or a muscarinic agonist oxotremorine as a reference for 7 and 14 days. AChE activity was markedly decreased in the three regions 1 day after the treatment with DDVP for 7 and 14 days with a gradual recovery 6 to 11 days, and much less decreased 1, 6 and 11 days after the treatment with propoxur for 7 days but not for 14 days in the hippocampus and cortex. The binding of [(3)H]-QNB, PZP and AF-DX 384 in the three regions was generally decreased by the treatment with DDVP for 7 and 14 days. Such down-regulations were generally restored 6 or 11 days after the treatment for 7 but not for 14 days. The down-regulation or up-regulation as measured by [(3)H]-QNB, PZP and AF-DX 384 was observed 1, 6 or 11 days after treatment with propoxur for 7 days and/or 14 days. Repeated treatment with oxotremorine produced similar effects except AChE activity to DDVP. These results suggest that repeated inhibition of AChE activity may usually cause down-regulation of mAChRs with some exception in the hippocampus when a reversible antiChE propoxur is injected.
Kobayashi
Haruo
H
Department of Veterinary Medicine, Faculty of Agriculture, Iwate University, 3-18-8 Ueda, Morioka 020-8550, Japan. hk1664@iwate-u.ac.jp <hk1664@iwate-u.ac.jp>
Suzuki
Tadahiko
T
Sakamoto
Maki
M
Hashimoto
Wataru
W
Kashiwada
Keiko
K
Sato
Itaru
I
Akahori
Fumiaki
F
Satoh
Tetsuo
T
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004006:Dichlorvos / Q000633:toxicity*; D008024:Ligands; D008297:Male; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000201:enzymology / Q000378:metabolism; D013997:Time Factors
D002800:Cholinesterase Inhibitors; D008024:Ligands; D011976:Receptors, Muscarinic; D004006:Dichlorvos; D000110:Acetylcholinesterase