HIGH AMMONIA LEVELS DECREASE BRAIN ACETYLCHOLINESTERASE ACTIVITY BOTHIN-VIVO AND IN-VITRO

We have tested the effect of ammonium injection on the activity of ace tylcholinesterase in rat brain. Fifteen minutes after ip injection of 7 mmol/kg of ammonium acetate, the activity of acetylcholinesterase in brain was reduced significantly. The inhibitory effect varied in a wi de range, with a maximum decrease of 60%, and was proportional to the concentration of ammonia reached in the brain. It is also shown that a mmonium salts added in vitro to the assay mixture inhibit acetylcholin esterase in brain homogenates competitively. The K-i values for inhibi tion of the enzyme in vitro were 7.2 and 8.5 mM for ammonium acetate a nd ammonium chloride, respectively, when ace- tylcholinesterase was as sayed in rat brain homogenates, and 7.6 and 8.3 mM when assayed in mic e brain homogenates. These results suggest that at least part of the n eurologic effects of ammonia could be mediated by an increase of acety lcholine as a consequence of the inhibition of acetylcholinesterase.