The effect of (a) neomycin and lactulose treatment on systemic and portal serum GABA levels in rats and (b) pH changes on [3H] GABA binding to isolated rat hepatocytes.
Recently it has been suggested that gamma-aminobutyric acid (GABA), a potent inhibitory neurotransmitter, may be involved in the pathogenesis of hepatic encephalopathy. If so, then therapeutic interventions that are known to improve or exacerbate the encephalopathic state should have significant effects on GABA homeostasis. In the present study, we determined the effect of neomycin and lactulose treatment on systemic and portal venous blood GABA levels in healthy rats and rats having undergone common bile duct ligation. We also studied the effect of alterations in extracellular pH on [3H]GABA binding to isolated rat hepatocytes. The results of the study revealed that systemic serum GABA levels in neomycin (0.38 +/- 0.09 mumoles/L: mean +/- SEM) and lactulose (0.45 +/- 0.11 mumoles/L) treated healthy rats were significantly lower than in healthy controls (0.63 +/- 0.21 mumoles/L, p less than 0.01 and 0.05 respectively). The same was true of portal venous GABA levels (1.02 +/- 0.29, 1.14 +/- 0.69 vs 3.44 +/- 1.6 mumoles/L respectively). In liver diseased rats however, systemic serum GABA levels in neomycin (2.35 +/- 0.22 mumoles/L) and lactulose (1.92 +/- 0.29 mumoles/L) treated rats were similar to those in untreated liver disease controls (2.36 +/- 0.22 mumoles/L) as were portal venous GABA levels (5.76 +/- 0.73, 2.91 +/- 0.46 vs. 3.82 +/- 0.47 mumoles/L respectively). [3H]GABA binding to isolated hepatocytes was significantly decreased (46%) in the presence of an alkaline extracellular environment. The results of this study indicate that, in healthy but not in liver diseased rats, peripheral GABA homeostasis is altered by agents or factors that are known to improve or exacerbate the encephalopathic state in humans.
Minuk
G Y
GY
Division of Gastroenterology, University of Calgary, Alberta.
Sarjeant
E J
EJ
D000818:Animals; D003135:Common Bile Duct / Q000502:physiology; D004187:Disaccharides / Q000494:pharmacology*; D006501:Hepatic Encephalopathy / Q000209:etiology; D006706:Homeostasis; D006863:Hydrogen-Ion Concentration; D007792:Lactulose / Q000494:pharmacology*; D008026:Ligation; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism; D008297:Male; D009355:Neomycin / Q000494:pharmacology*; D011169:Portal Vein; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000097:blood* / Q000378:metabolism
D004187:Disaccharides; D007792:Lactulose; D005680:gamma-Aminobutyric Acid; D009355:Neomycin