Linked Life Data

3707603

Source:http://linkedlifedata.com/resource/pubmed/id/3707603

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1986-6-18
pubmed:abstractText
Para-chloroamphetamine (PCA) is selectively toxic to serotonergic neurons in laboratory animals. Acute, reversible neurotoxicity is followed by long-term effects which include inactivation of tryptophan hydroxylase and destruction of neurons. We have studied the metabolic formation of reactive intermediates that might be involved in long-term PCA neurotoxicity. Incubation of [3H]PCA with rat hepatic microsomes resulted in NADPH-dependent and oxygen-dependent covalent binding of radioactivity to microsomal protein. Addition of SKF-525A and glutathione to incubation mixtures inhibited [3H]PCA covalent binding 30% and 92% respectively. No inhibition of radiolabeled covalent binding was observed in an atmosphere of carbon monoxide/oxygen (80/20). 7,8-Benzoflavone was more effective than metyrapone in inhibiting [3H]PCA covalent binding. The extent of [3H]PCA covalent binding to microsomal protein was unchanged after phenobarbital pretreatment of rats, whereas 3-methylcholanthrene pretreatment increased [3H]PCA covalent binding (175%). NADPH-dependent and oxygen-dependent covalent binding of radioactivity was also observed when [3H]PCA was incubated with rat brain microsomal preparations. Addition of SKF-525A and glutathione to incubation mixtures inhibited covalent binding 10 and 40% respectively. There were no significant differences in total, NADPH-independent or NADPH-dependent covalent binding of radiolabeled R,S(+/-)-, R(-)-, or S(+)-PCA to rat hepatic microsomal protein. Less covalent binding was observed when [3H]amphetamine was incubated with rat liver microsomal preparations as compared to results with [3H]PCA. Minimal covalent binding was observed when [3H]PCA was incubated with liver microsomal preparations from rabbits, a species resistant to PCA neurotoxicity. Results of these metabolism studies are consistent with the hypothesis that oxidative metabolic activation of PCA to reactive and toxic metabolites is related to the long-term neurotoxicity of this agent.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1737-42
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1986
pubmed:articleTitle
Metabolic activation of the serotonergic neurotoxin para-chloroamphetamine to chemically reactive intermediates by hepatic and brain microsomal preparations.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S.