Ammonia-induced upregulation of peripheral-type benzodiazepine receptors in cultured astrocytes labeled with [ 3H]PK 11195

Abstract

Evidence suggests that peripheral-type benzodiazepine receptors (PBRs) may play a role in hepatic encephalopathy (HE), a condition associated with increased levels of ammonia in brain. In the present study, the regulation of [ 3H]PK 11195-binding to PBRs in cultured rat astrocytes that had been previously exposed to NH 4Cl was investigated. 24 h treatment of 21–28-day-old cultures with 2, 5 or 10 mM NH 4Cl resulted in 25 ± 3, 48 ± 3 and 42 ± 4% increase in the number of [ 3H]PK 11195-binding sites, respectively. No further change in [ 3H]PK 11195-binding was observed after exposure of astrocytes to 5 mM NH 4Cl for 48 or 72 h. Ammonia treatment did not cause any significant alteration in the affinity of [ 3H]PK 11195 for PBRs. The present study demonstrates the susceptibility of the PK 11195-binding site of PBRs in cultured astrocytes to ammonia and suggests that increase in brain ammonia concentration causes a supersensitivity of PBRs.