Abstract/Details

Effect of chlorpyrifos oxon on M2 muscarinic acetylcholine receptor regulation


2004 2004

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Abstract (summary)

A primary mechanism of tolerance to anticholinesterases is downregulation of muscarinic receptors. Activation of muscarinic receptors leads to receptor regulation via a sequential pathway involving desensitization, internalization and downregulation. The initial step in M2 receptor desensitization is phosphorylation by G-protein Receptor Kinase 2 (GRK2). Our laboratory previously noted that the potent anticholinesterase chlorpyrifos oxon (CPO) can inhibit agonist-mediated phosphorylation of human recombinant M2 receptors by GRK2 in vitro while paraoxon, another structurally-related anticholinesterase, had no effect. We hypothesized that CPO can disrupt M2 receptor regulation through direct binding to the M2 receptor at the GRK2-mediated phosphorylation site. To test the hypothesis, the binding of a radiolabeled muscarinic agonist and surface-selective antagonist were measured in cell lines expressing M2 receptors. Immunocytochemistry using M2 subtype-specific antibody was also done to determine the location of M2 receptors after treatments with carbachol and CPO in rat striatal neurons. (Abstract shortened by UMI.)

Indexing (details)


Subject
Toxicology;
Pharmacology;
Cellular biology
Classification
0383: Toxicology
0419: Pharmacology
0379: Cellular biology
Identifier / keyword
Health and environmental sciences; Biological sciences
Title
Effect of chlorpyrifos oxon on M2 muscarinic acetylcholine receptor regulation
Author
Udarbe, Elmar Mabunga
Number of pages
99
Publication year
2004
Degree date
2004
School code
0664
Source
MAI 43/04M, Masters Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780496922482, 0496922483
Advisor
Pope, Carey N.
University/institution
Oklahoma State University
University location
United States -- Oklahoma
Degree
M.S.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
1424861
ProQuest document ID
305078595
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/305078595
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