Abstract：
: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 3H-PK 11195 in cultured astrocytes following chronic exposure to manganese. When astrocytes were exposed to 100 microM manganese for 1 week, a 57% increase in Bmax for 3H-PK 11195 binding was detected (P < 0.01) with no change in the Kd 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 PTBR mRNA levels following manganese treatment. These findings suggest that manganese up-regulates 3H-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.
journal_name
Neurosci Lettjournal_title
Neuroscience lettersauthors
Hazell AS,Desjardins P,Butterworth RFdoi
10.1016/s0304-3940(99)00489-9keywords:
subject
Has Abstractpub_date
1999-08-13 00:00:00pages
5-8issue
1eissn
0304-3940issn
1872-7972pii
S0304394099004899journal_volume
271pub_type
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