AMMONIA-INDUCED UP-REGULATION OF PERIPHERAL-TYPE BENZODIAZEPINE RECEPTORS IN CULTURED ASTROCYTES LABELED WITH [H-3] PK-11195

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 [H-3]PK 11195-binding to PBRs in cultured rat astrocytes that had been previously exposed to NH4Cl was investigated. 24 h treatment of 21-28-day-old cultures with 2, 5 or 10 mM NH4Cl resulted in 25 +/- 3, 48 +/- 3 and 42 +/- 4% increase in the number of [H-3]PK 11195-binding sites, respectively. No further change in [H-3]PK 11195-binding was observed after exposure of astrocytes to 5 mM NH,CI for 48 or 72 h. Ammonia treatment did not cause any significant alteration in the affinity of [H-3]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.