Linked Life Data

8937895

Source:http://linkedlifedata.com/resource/pubmed/id/8937895

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-3-10
pubmed:abstractText
High, subcutaneous doses of the organophosphorus insecticide chlorpyrifos (CPF) in adult male rats can be well-tolerated despite extensive and persistent acetylcholinesterase (AChE) inhibition. We propose that changes in acetylcholine synthesis could modulate the toxicity associated with extensive AChE inhibition following CPF exposure. High-affinity choline uptake (HACU, the rate-limiting step in acetlcholine synthesis) and binding to [3H]-hemicholinium-3 (HC-3, a specific ligand for the choline transporter) were chosen as indicators of acetylcholine synthesis. Female, Sprague-Dawley rats (220-280 g) were treated with either vehicle (peanut oil, 2 ml/kg, sc) or CPF (280 mg/kg, 2 ml/kg, sc), examined daily for clinical signs of toxicity, and sacrificed 1, 2, or 7 days later for neurochemical measurements (AChE inhibition, muscarinic receptor binding using [3H]quinuclidinyl benzilate (QNB) and [3H]cis-methyldioxolane (CD) as ligands, HACU and [3H]HC-3 binding) in frontal cortex. Despite extensive AChE inhibition (90-93%) at all time points, relatively minor degrees of overt toxicity were noted in CPF-treated rats. Binding to the non-selective muscarinic antagonist [3H]QNB was reduced (10-34%), whereas binding to the putative m2-selective agonist [3H]CD was increased (15-23%) at all three time points. HACU was reduced (20%) in crude synaptosomes prepared from CPF-treated rats 1 day following exposure but no significant changes were noted at 2 or 7 days after treatment. CPF-oxon, the active oxidative metabolite of CPF, was a weak inhibitor of HACU in vitro (IC50 > 200 microM). Binding to [3H]HC-3 was reduced in a dose-related manner 1 day after CPF exposure. Kinetic analyses of [3H]HC-3 binding 1 day after CPF (280 mg/kg) indicated a significant reduction in density (Bmax: control, 187 +/- 18 fmol/mg protein; CPF, 104 +/- 12 fmol/mg protein) with no apparent change in binding affinity (Kd: control, 25 +/- 3 nM; CPF, 19 +/- 3 nM). These results suggest that a reduction in HACU/acetylcholine synthesis may contribute, along with compensatory changes in cholinergic receptors, to the diminished toxicity following extensive AChE inhibition by CPF.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0272-0590
pubmed:author
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
84-90
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Effects of chlorpyrifos on high-affinity choline uptake and [3H]hemicholinium-3 binding in rat brain.
pubmed:affiliation
Division of Toxicology, College of Pharmacy and Health Sciences, Northeast Louisiana University, Monroe 71209-0470, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.