Ammonia and methionine sulfoximine intoxication.
Intoxication  with ammonium acetate abolished the suppression of action potential generation by cortical postsynaptic inhibition, i.e. produced 'disinhibition', due to the inactivation of neuronal Cl- extrusion. With the occurrence of disinhibition cerebral ammonia increased to 445% of normal; glutamine increased to 170%. Methionine sulfoximine (MSO), an inhibitor of glutamine synthetase, produced disinhibition about 3 h after administration; at this time cerebral ammonia was increased to 290% of normal, glutamine was unchanged. Intoxication with MSO for less than 3 h significantly decreased the amount of ammonium acetate needed to produce disinhibition at cerebral ammonia concentrations ot 340-430% of normal. MSO produces an endogenous ammonia intoxication which: (i) decreases the amount of exogenous ammonia required to affect cortical postsynaptic inhibitions; and (ii) eventually becomes sufficiently severe to disturb cortical inhibitory neuronal interactions by itself.
D000085:Acetates / Q000633:toxicity*; D000200:Action Potentials / Q000187:drug effects; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002415:Cats; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects; D008717:Methionine Sulfoximine / Q000633:toxicity*; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology
D000085:Acetates; D008717:Methionine Sulfoximine; D000641:Ammonia; C018824:ammonium acetate