Brain regional acetylcholinesterase activity and muscarinic acetylcholine receptors in rats after repeated administration of cholinesterase inhibitors and its withdrawal

Journal Article · Thu Mar 15 04:00:00 EDT 2007 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2006.11.006· OSTI ID:20976880

Kobayashi, Haruo ^[1]; Suzuki, Tadahiko ^[1]; Sakamoto, Maki ^[2]; Hashimoto, Wataru ^[3]; Kashiwada, Keiko ^[1]; Sato, Itaru ^[1]; Akahori, Fumiaki ^[4]; Satoh, Tetsuo ^[5]

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1. Department of Veterinary Medicine, Faculty of Agriculture, Iwate University, 3-18-8 Ueda, Morioka 020-8550 (Japan)
2. Kyoritsu Seiyaku Corporation, 2-9-22 Takamihara, Tsukuba, Ibaraki 300-1252 (Japan)
3. City of Sendai Economic Affairs Bureau Agricultural Promotion Section, 3-7-1 Kokubuncho, Aoba-ku, Sendai 980-8671 (Japan)
4. Department of Pharmacology, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara 229-8501 (Japan)
5. Tokyo Dental College Ichikawa General Hospital Cornea Center, 5-11-13 Sugano, Ichikawa, Chiba 272-8513 (Japan)

Activity of acetylcholinesterase (AChE) and specific binding of [{sup 3}H]quinuclidinyl benzilate (QNB), [{sup 3}H]pirenzepine (PZP) and [{sup 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 [{sup 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 [{sup 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.

• OSTI ID: 20976880
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2-3 Vol. 219; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACETYLCHOLINE
CARBAMATES
CHOLINESTERASE
HIPPOCAMPUS
RATS
RECEPTORS
TRITIUM