Chronic exposure of rat primary astrocyte cultures to manganese results in increased binding sites for the 'peripheral-type' benzodiazepine receptor ligand 3H-PK 11195

Alterations of 'peripheral-type' benzodiazepine receptors (PTBRs) in brain are a feature of hepatic encephalopathy (HE). Although ammonia toxicity has been implicated in the disorder, recent findings suggest an accumulation of manganese in the brains of cirrhotic patients dying in hepatic coma. In this study, we examined the expression of PTBRs as well as the binding of the selective PTBR ligand H-3-PK 11195 in cu Itu red astrocytes following chronic exposure to manganese. When astrocytes were exposed to 100 mu M manganese for 1 week, a 57% increase in B-max for H-3-PK 11195 binding was detected (P < 0.01) with no change in the K-d value. However, an examination by RT-PCR of the expression of the isoquinoline-binding moiety of the PTBR complex in these cells revealed no change in PIER mRNA levels following manganese treatment. These findings suggest that manganese up-regulates H-3-PK 11195 binding sites by a process which does not involve a change in transcription. In view of the proposed role of astrocytic PTBRs in 'neurosteroid' synthesis, manganese-induced increases of PTBRs could contribute to the pathogenesis of HE. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.