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

Journal Article · · Toxicology and Applied Pharmacology
 [1];  [1];  [2];  [3];  [1];  [1];  [4];  [5]
  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, Vol. 219, Issue 2-3; Other Information: DOI: 10.1016/j.taap.2006.11.006; PII: S0041-008X(06)00420-0; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
Country of Publication:
United States
Language:
English