Effects of ammonia and hepatic failure on the net efflux of endogenous glutamate, aspartate and taurine from rat cerebrocortical slices: modulation by elevated K+ concentrations.
Cerebrocortical minislices derived from control rats ("control slices") and from rats with thioacetamide (TAA)-induced hepatic failure showing moderate hyperammonemia and symptoms of hepatic encephalopathy (HE) ("HE slices"), were incubated with physiological saline in the absence or presence of 5 mM ammonium acetate ("ammonia"), at potassium ion (K+) concentrations ranging from 5 to 15 mM. The efflux of endogenous aspartate (Asp), glutamate (Glu) and taurine (Tau) to the incubation medium was assayed by HPLC. At 5 mM K+, perfusion of control slices with ammonia did not affect Glu and slightly depressed Asp efflux. Raising K+ concentrations in the incubation medium to 7.5 led to inhibition of Glu and Asp efflux by ammonia and the inhibitory effect was further potentiated at 10 mM K+. The inhibition was also significant at 15 mM K+. This suggests that, depression of excitatory neurotransmission associated with acute hyperammonemia is more pronounced under conditions of intense neuronal activity than in the resting state. HE moderately increased the efflux of Glu and Asp, and the stimulatory effect of HE on Glu and Asp efflux showed virtually no variation upon changing K+ concentration up to 15 mM. Ammonia strongly, and HE moderately, increased Tau efflux at 5 mM K+. However, both the ammonia- and HE-dependent Tau efflux decreased with increasing K+ concentration in the medium and was no longer significant at 10 mM concentration, indicating that intense neuronal activity obliterates the neuroprotective functions of this amino acid triggered by hyperammonemia.
Zielińska
M
M
Department of Neurotoxicology, Medical Research Centre, Polish Academy of Sciences, Pawińskiego St. 5, 02-106, Warsaw, Poland.
Hilgier
W
W
Law
R O
RO
Gorynski
P
P
Albrecht
J
J
D000641:Ammonia / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D017093:Liver Failure / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000378:metabolism*
D013654:Taurine; D001224:Aspartic Acid; D018698:Glutamic Acid; D000641:Ammonia; D011188:Potassium