Induction of peripheral-type benzodiazepine receptors in mouse brain following thioacetamide-induced acute liver failure.
To investigate the possible role of peripheral-type benzodiazepine receptors (PBR) in hepatic encephalopathy, we examined expression of PBR in mouse brain following thioacetamide (TAA)-induced acute liver failure. Treatment of mice with TAA resulted in an increase in the number of binding sites of the PBR ligand [3H] Ro5-4864 to brain homogenates, with no significant change in affinity of the ligand. The order of potency of different ligands to compete against [3H] Ro5-4864 binding in the brain of TAA-treated mice was Ro5-4864 > PK11195 > diazepam > protoporphyrin IX, findings similar to those in the control. Northern blot analysis revealed an increase in PBR/isoquinoline binding protein (PBR/IBP) mRNA in mouse brain following TAA treatment, in a time- and dose-dependent manner. These results indicate that the increased number of PBR in the brains of TAA-treated mice relates to the induction of PBR/IBP expression and suggest that the induction of PBR in brain may contribute to pathogenesis of hepatic encephalopathy.
Kadota
Y
Y
Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Inoue
K
K
Tokunaga
R
R
Taketani
S
S
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003164:Competitive Bidding; D004305:Dose-Response Relationship, Drug; D005260:Female; D017114:Liver Failure, Acute / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000378:metabolism*; D013853:Thioacetamide / Q000494:pharmacology*; D013997:Time Factors
D011963:Receptors, GABA-A; D013853:Thioacetamide