Acute liver failure and hyperammonemia increase peripheral-type benzodiazepine receptor binding and pregnenolone synthesis in mouse brain

被引:74
作者
Itzhak, Y
RoigCantisano, A
Dombro, RS
Norenberg, MD
机构
[1] UNIV MIAMI,SCH MED,DEPT BIOCHEM,MIAMI,FL 33101
[2] UNIV MIAMI,SCH MED,DEPT MOLEC BIOL,MIAMI,FL 33101
[3] UNIV MIAMI,SCH MED,DEPT PATHOL D33,MIAMI,FL 33101
[4] UNIV MIAMI,SCH MED,DEPT SURG,MIAMI,FL 33101
[5] VET ADM MED CTR,MIAMI,FL 33125
关键词
hepatic encephalopathy; ammonia; thioacetamide; peripheral benzodiazepine receptor; pregnenolone; neurosteroid;
D O I
10.1016/0006-8993(95)01244-3
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We investigated the role of brain peripheral-type benzodiazepine receptors (PBRs) and pregnenolone (a product of PBRs activation) in hepatic encephalopathy (HE)/hyperammonemia. Administration of the hepatotoxin, thioacetamide, or ammonium acetate to mice for 3 days significantly increased the number of brain PBRs (138-146% of control) and the affinity of the ligands for these receptors (2-fold). The total content of pregnenolone and its rate of synthesis in brain of the experimental animals were significantly increased. Our results suggest a novel integrated mechanism by which ammonia-induced activation of PBRs leads to elevated levels of pregnenolone-derived neurosteroids which are known to enhance GABA-ergic neurotransmission. This mechanism may play a pivotal role in pathogenesis of HE.
引用
收藏
页码:345 / 348
页数:4
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