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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1996-10-24
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pubmed:abstractText |
A third-generation pharmacokinetic/pharmacodynamic model was proposed for receptor/gene-mediated corticosteroid effects. The roles of the messenger RNA (mRNA) for the glucocorticoid receptor (GR) in hepatic GR down-regulation and the mRNA for hepatic tyrosine aminotransferase (TAT) induction by methylprednisolone (MPL) were examined. Male adrenalectomized Wistar rats received 50 mg/kg MPL iv. Blood and liver samples were collected at various time points for a period of 18 hr. Plasma concentrations of MPL, free hepatic cytosolic GR densities, GR mRNA, TAT mRNA, and TAT activities in liver were determined. Plasma MPL profile was biexponential with a terminal t1/2 of 0.57 hr. Free hepatic GR density rapidly disappeared from cytoplasm after the MPL dose and then slowly returned to about 60% of starting level after 16 hr. Meanwhile, GR mRNA level fell to 45% of baseline within 2 hr postdosing, and remained at that level for at least 18 hr. The GR down-regulation of GR mRNA and protein turnover rate were modeled. The TAT mRNA began to increase at about 2 hr, reached a maximum at about 5 hr, and declined to baseline by 14 hr. TAT induction followed a similar pattern, except the induction was delayed about 0.5 hr. Pharmacodynamic parameters were obtained by fitting seven differential equations in a piecewise fashion. The cascade of corticosteroid steps were modeled by a series of inductions for steroid-receptor-DNA complex, two intermediate transit compartments, TAT mRNA, and TAT activity. Results indicate that GR mRNA and TAT mRNA are major controlling factors for the receptor/gene-mediated effects of corticosteroids.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenal Cortex Hormones,
http://linkedlifedata.com/resource/pubmed/chemical/Glucocorticoids,
http://linkedlifedata.com/resource/pubmed/chemical/Methylprednisolone,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucocorticoid,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine Transaminase
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0090-466X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
163-81
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8719235-Adrenal Cortex Hormones,
pubmed-meshheading:8719235-Adrenalectomy,
pubmed-meshheading:8719235-Animals,
pubmed-meshheading:8719235-Blotting, Northern,
pubmed-meshheading:8719235-Glucocorticoids,
pubmed-meshheading:8719235-Kinetics,
pubmed-meshheading:8719235-Liver,
pubmed-meshheading:8719235-Male,
pubmed-meshheading:8719235-Methylprednisolone,
pubmed-meshheading:8719235-Models, Biological,
pubmed-meshheading:8719235-RNA, Messenger,
pubmed-meshheading:8719235-Rats,
pubmed-meshheading:8719235-Rats, Wistar,
pubmed-meshheading:8719235-Receptors, Glucocorticoid,
pubmed-meshheading:8719235-Tyrosine Transaminase
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pubmed:year |
1995
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pubmed:articleTitle |
Third-generation model for corticosteroid pharmacodynamics: roles of glucocorticoid receptor mRNA and tyrosine aminotransferase mRNA in rat liver.
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pubmed:affiliation |
Department of Pharmaceutics, State University of New York at Buffalo 14260, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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