Linked Life Data

7748185

Source:http://linkedlifedata.com/resource/pubmed/id/7748185

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1995-6-9
pubmed:abstractText
Recent investigations demonstrated that administration of 1-aminobenzotriazole (ABT) to rats caused adrenal gland enlargement. Studies were done to pursue the mechanism(s) involved. Preliminary experiments revealed that the adrenal enlargement caused by ABT was associated with a decline in plasma corticosterone concentrations, suggesting inhibition of adrenal steroidogenesis. Indeed, a single injection of ABT (25 or 50 mg/kg body weight) to rats caused concentration-dependent declines (60-80%) in adrenal mitochondrial and microsomal cytochrome P450 (P450) concentrations. The decreases in adrenal P450 levels exceeded those in hepatic microsomes. Accompanying the declines in adrenal P450 concentrations were decreases in steroid hydroxylase activities. Mitochondrial 11 beta-hydroxylase and cholesterol side-chain cleavage activities and microsomal 21-hydroxylase activity were diminished markedly (60-90%) by ABT treatment. In contrast, activity of adrenal 3 beta-hydroxysteroid dehydrogenase-isomerase was not affected by ABT, indicating specificity for P450-dependent reactions. Incubation of adrenal microsomes or mitochondria in vitro with ABT plus an NADPH-generating system had no effect on P450 concentrations or on steroid hydroxylase activities. Similar incubations with hepatic microsomes caused declines in P450 levels and in the rates of P450-mediated xenobiotic metabolism. The results demonstrate that ABT is a potent inhibitor of adrenal steroid hydroxylases in vivo, but the in vitro studies indicate that the mechanism of action differs from that on other P450 isozymes. The absence of inhibitor effects in vitro suggests that an extra-adrenal metabolite of ABT is responsible for the in vivo inactivation of steroidogenic enzymes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1057-62
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Inactivation of adrenal cytochromes P450 by 1-aminobenzotriazole. Divergence of in vivo and in vitro actions.
pubmed:affiliation
Department of Pharmacology and Toxicology, Philadelphia College of Pharmacy and Science, PA 19104, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't