AMMONIUM ACETATE INHIBITS IONOTROPIC RECEPTORS AND DIFFERENTIALLY AFFECTS METABOTROPIC RECEPTORS FOR GLUTAMATE

The effects of ammonium salts in concentration similar to those found in plasma in course of hepatic encephalopathy (2-4 mM) were studied in brain slices in order to clarify how glutamate synapses are affected by this pathological situation. Electrophysiological (mice cortical we dge preparations) and biochemical techniques (inositol phosphates and cyclic AMP measurements) were used so that the function of both the io notropic and metabotropic glutamate receptors was evaluated. Ammonium acetate (2-4 mM), but not sodium acetate reduced the degree of depolar ization of cortical wedges induced by different concentrations of N-me thyl-D-aspartic acid (NMDA) or alphaAmino-3-hydroxy-5-methyl-4-isoxazo lepropionic acid (AMPA). This reduction was non-competitive in nature and did not reverse during the experimental period (90 min). In a simi lar manner, ammonium acetate reduced the formation of inositol phospha tes induced by (1S,3R)-1-amynocyclopentane-1,3-dicarboxylic acid (1S,3 R-ACPD) (100 mu M), the prototype agonist of metabotropic glutamate re ceptors. When the metabotropic glutamate receptors negatively linked t o the forskolin-stimulated cyclic AMP formation were evaluated, ammoni um acetate significantly hampered forskolin effects and its actions we re additive with those of the metabotropic glutamate receptor agonist 1S,3R-ACPD. In conclusion, our results suggest that toxic concentratio ns of ammonium impair the function of glutamate receptors of NMDA and AMPA type and of the metabotropic glutamate receptors linked to inosit ol phosphate formation while they functionally potentiate the action o f glutamate agonists on the receptors negatively linked to adenylyl cy clase.