Ammonia and methionine sulfoximine intoxication

Abstract

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.