Evidence for the presence of a benzodiazepine receptor binding substance in cerebrospinal fluid of a rabbit model of hepatic encephalopathy.
Based on the reversal of hepatic encephalopathy in animal models with administration of specific benzodiazepine receptor antagonists, it has been postulated that this syndrome may be mediated by an endogenous benzodiazepine-like compound. In this study using a radio-receptor assay, evidence for the existence of this substance has been demonstrated in cerebrospinal fluid but not sera of rabbits with hepatic encephalopathy due to galactosamine-induced hepature failure. Cerebrospinal fluid from rabbits with hepatic encephalopathy caused 36.1 +/- 5.03% displacement of 3H-Ro 15-1788 specific binding to cortical benzodiazepine receptors, compared to 11.7 +/- 0.76% in control animals (P less than 0.01). The benzodiazepine receptor binding activity has been shown to behave as a competitive inhibitor of radiolabeled benzodiazepine receptor binding. The finding of endogenous benzodiazepine binding activity affords a potential explanation for the amelioration of hepatic encephalopathy in this model with the administration of benzodiazepine receptor antagonists.
Mullen
K D
KD
Department of Medicine, Cleveland Metropolitan General Hospital, Case Western Reserve University, Ohio 44109.
Martin
J V
JV
Mendelson
W B
WB
Kaminsky-Russ
K
K
Jones
E A
EA
D000614:Aminocaproates / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D005442:Flumazenil / Q000378:metabolism; D058787:GABA-A Receptor Antagonists; D005688:Galactosamine; D006501:Hepatic Encephalopathy / Q000134:cerebrospinal fluid* / Q000139:chemically induced; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000134:cerebrospinal fluid; D008297:Male; D011817:Rabbits; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000378:metabolism; D020888:Vigabatrin
D000614:Aminocaproates; D058787:GABA-A Receptor Antagonists; D007042:Hypoxanthines; D011963:Receptors, GABA-A; D019271:Hypoxanthine; D005442:Flumazenil; D005688:Galactosamine; D020888:Vigabatrin