THE EFFECT OF GAMMA-AMINOBUTYRIC-ACID ON HEPATIC REGENERATIVE ACTIVITY FOLLOWING PARTIAL-HEPATECTOMY IN RATS

Background: γ-Aminobutyric acid (GABA) is a potent inhibitory neurotransmitter with growth-regulatory properties. In fulminant hepatic failure, a condition in which hepatic regeneration may be impaired, systemic serum GABA concentrations are markedly elevated. The present study was designed to determine whether increased amounts of circulating GABA interfere with hepatic regenerative activity. Methods: Exogenous GABA or isotonic saline was administered to adult male rats (n = 6 - 12/group) 16 hours before partial hepatectomy and twice daily for 1-3 days thereafter. The hypertrophic and hyperplastic components of hepatic regeneration were determined by calculation of the restitution of liver mass, [14C]leucine incorporation into protein (protein synthesis), and [3H]thymidine incorporation into hepatic DNA (DNA synthesis). Results: Exogenous GABA impaired restitution of liver mass (GABA vs. controls, day 3: 76% ± 7% vs. 90% ± 9%, mean ± SD) (P < 0.005) and the rate of protein synthesis (GABA vs. controls, day 1: 379 ± 39 dpm/mg protein vs. 564 ± 67 dpm/mg protein) (P < 0.01) without interfering with DNA synthesis. Supplemental administration of corticosterone and putrescine restored protein synthesis rates to normal in GABA-treated rats. Conclusions: These results indicate that elevated serum GABA concentrations interfere with the hypertrophic component of hepatic regeneration following partial hepatectomy in rats. © 1993.