Ammonia added in vitro, but not moderate hyperammonemia in vivo, stimulates glutamate uptake and H(+)-ATPase activity in synaptic vesicles of the rat brain.
The uptake of radiolabelled neurotransmitters: glutamate (GLU), GABA, and dopamine (DA) and the activity of the vacuolar type H(+)-pumping ATPase (H(+)-ATPase), were measured in crude synaptic vesicles treated in vitro with a neurotoxic (3 mM) dose of NH4+ (acetate or chloride), or isolated from rats with a moderate increase of brain ammonia (to approximately 0.6 mM) induced by i.p. administration of ammonium acetate (HA rats) or a hepatotoxin-thioacetamide (HE rats). In vitro treatment with ammonium salts increased the sodium-independent, chloride-dependent uptake of GLU but did not stimulate the uptake of GABA or DA. The in vitro treatment also stimulated the H(+)-ATPase activity. Since H(+)-ATPase generates the electrochemical gradient driving synaptic vesicular neurotransmitter transport, its stimulation by ammonia may have facilitated GLU uptake. However the GLU specificity of the effect must be related to other factors differentially affecting GLU uptake and the uptake of other neurotransmitters. Enhanced GLU accumulation in the synaptic vesicles may contribute to the increase of synaptic GLU exocytosis previously reported to accompany acute increases of brain ammonia to toxic levels. However, GLU uptake and H(+)-ATPase activity, but also the uptake of GABA and DA, were unchanged in synaptic vesicles prepared from rats with HA or HE. This indicates that changes in GLU and/or GABA release reported for moderate hyperammonemic conditions must be elicited by factors unrelated to the synaptic vesicular transport of the amino acids.
Albrecht
J
J
Department of Neuropathology, Polish Academy of Sciences.
Hilgier
W
W
Walski
M
M
D000641:Ammonia / Q000097:blood / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013572:Synaptic Vesicles / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000641:Ammonia; D006180:Proton-Translocating ATPases