Effect of phenol and sodium octanoate on the astrocyte benzodiazepine receptor.
Alterations in the benzodiazepine (BZD) receptor system have been proposed as key factors in the pathogenesis of hepatic encephalopathy (HE). To date, the focus of research has been exclusively on the central-type neuronal receptor. However, astrocytes also possess BZD receptors which are of the peripheral-type. In recent studies we found an increased affinity of the astrocyte BZD receptor, using [3H]Ro5-4864 as the ligand, after treatment of cell cultures with ammonia, an agent strongly implicated in HE. The present study was undertaken to determine whether other suspected toxins in HE (phenol and octanoic acid) produce comparable effects. Scatchard analysis of the binding of [3H]Ro5-4864 to astrocyte homogenates showed a significant decrease in Bmax in cells that had been treated with 0.5, 1.0 and 3.0 mM phenol (46%, 58% and 68%, respectively). The same homogenates also showed a significant decrease in Kd after treatment with 0.5 mM phenol. No change in either affinity or receptor number was seen with 0.5, 1.0 and 3.0 mM sodium octanoate. Our results indicate that phenol, but not sodium octanoate, has an effect on the astrocyte BZD receptor. Thus, different agents that have been implicated in HE produce varying effects on the astrocytic BZD receptor. These findings suggest that the astrocyte benzodiazepine receptor may be involved in the pathogenesis of HE.
Ducis
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Department of Pathology, University of Miami/Jackson Memorial Hospital, FL.
Norenberg
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Norenberg
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D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001570:Benzodiazepinones / Q000378:metabolism*; D002210:Caprylates / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology*; D019800:Phenol; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*
D001570:Benzodiazepinones; D002210:Caprylates; D009498:Neurotoxins; D010636:Phenols; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D019800:Phenol