Ammonia-induced upregulation of peripheral-type benzodiazepine receptors in cultured astrocytes labeled with [3H]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 [3H]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 [3H]PK 11195-binding sites, respectively. No further change in [3H]PK 11195-binding was observed after exposure of astrocytes to 5 mM NH4Cl 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.
Itzhak
Y
Y
Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, FL.
Norenberg
M D
MD
D000643:Ammonium Chloride / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D007546:Isoquinolines / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344; D011955:Receptors, Drug / Q000096:biosynthesis / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*
D007546:Isoquinolines; D009419:Nerve Tissue Proteins; D011955:Receptors, Drug; C051898:isoquinoline receptor; D000643:Ammonium Chloride; D003994:Bucladesine; C037850:PK 11195