Plasma GABA, GABA-like activity and the brain GABA-benzodiazepine receptor complex in rats with chronic hepatic encephalopathy.
Plasma gamma-aminobutyric acid (GABA)-like activity, plasma GABA and the brain GABA-benzodiazepine receptor complex were studied in rats with chronic hepatic encephalopathy. Portal vein ligation (after prior subcutaneous transposition of the spleen) results in complete portal bypass of splanchnic blood. In addition, significant hepatocellular damage was superimposed on this model of portosystemic shunting by ligation of the common bile duct. Plasma GABA-like activity (determined by radioreceptor assay) and true plasma GABA concentrations (determined by high-performance liquid chromatography) were found to be significantly increased in both portal vein-ligated and portal vein and bile duct-ligated rats, compared with controls. However, plasma GABA-like activity was consistently greater than the concentration of true GABA in the plasma of all rats. This suggested the presence of a GABA-like factor in plasma that can inhibit [3H]GABA binding, but is not GABA itself. The concentration of this GABA-like factor was significantly increased in the plasma of rats with chronic hepatic encephalopathy. Despite the significant increase in plasma GABA-like activity and plasma GABA concentrations, there was no alteration in the affinity or density of the physiologically relevant, low-affinity brain GABA binding site in the rats with portal vein ligation, with or without bile duct ligation. There was also no significant alteration in brain benzodiazepine binding in these rats. GABA enhancement of benzodiazepine binding was unchanged in the portal vein-ligated rats. However, the maximal enhancement of benzodiazepine binding was decreased in the rats with portal vein and bile duct ligation. There appears to be no substantial evidence that brain GABAergic neurotransmission is increased in these models of chronic hepatic encephalopathy.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002908:Chronic Disease; D003135:Common Bile Duct; D005445:Flunitrazepam / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000378:metabolism*; D008026:Ligation; D008297:Male; D011169:Portal Vein; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000097:blood*
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam