The effect of GABA on serum and hepatic polyamine concentrations after partial hepatectomy in rats.
Serum and hepatic polyamine concentrations including putrescine, spermidine and spermine were documented at various time intervals after partial hepatectomy in rats treated with GABA (500 micrograms/gm body wt) or isotonic saline. Aside from a transient decrease in spermidine levels, GABA treatment had no effect on serum polyamine concentrations. In the liver, however, GABA treatment markedly attenuated the increase in hepatic putrescine concentrations that occurs after partial hepatectomy such that levels were 64%, 74% and 100% lower than in saline-treated controls on days 1, 2 and 3 after partial hepatectomy (p less than 0.005, p less than 0.01 and p less than 0.05, respectively). Spermidine and spermine concentrations in the liver were not affected by GABA treatment. To determine the mechanism whereby GABA lowers putrescine concentrations in regenerating liver, ornithine decarboxylase messenger RNA and enzyme activity were documented after GABA treatment. Although ornithine decarboxylase messenger RNA levels were similar, ornithine decarboxylase enzyme activity was significantly inhibited 12 hr after partial hepatectomy in GABA-treated rats compared with saline-treated controls. The results of this study indicate that GABA inhibits hepatic putrescine synthesis at a posttranscriptional level in rats after partial hepatectomy. These results could help to explain the impairment in hepatic regenerative activity that occurs in patients with elevated serum GABA concentrations and fulminant hepatic failure.
Liver Diseases Research Laboratory, University of Manitoba, Winnipeg, Canada.
G Y
GY
Minuk
T
T
Gauthier
A
A
Gaharie
L J
LJ
Murphy
D000818:Animals; D006498:Hepatectomy / Q000379:methods; D008099:Liver / Q000378:metabolism*; D008297:Male; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism; D009994:Osmolar Concentration; D011073:Polyamines / Q000097:blood* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*
D011073:Polyamines; D012333:RNA, Messenger; D005680:gamma-Aminobutyric Acid; D009955:Ornithine Decarboxylase