Effect of ammonia on amino acid uptake by brain microvessels

NH4+ ions, at a concentration (0.25 mM) similar to that found in the plasma of patients with hepatic encaphalopathy, cause, in vitro, a significant stimulation of the uptake by brain microvessels of large neutral amino acids, without any effect on the uptake of α-methylaminoisobutyric acid, glutamic acid, or lysine. Such a stimulation occurs essentially through an increase of the maximal transport capacity (V(max)) of the saturable component. It is apparently mediated by the intracellular formation of glutamine, which is then exchanged, through the L-system of transport, for large neutral amino acids such as leucine, phenylalanine, or tyrosine. At higher concentrations (≥0.5 mM), NH4+ ions cause also a decrease of carrier affinity for neutral amino acids, which counteracts the stimulatory effect on their uptake.