The Ammonia and Glutamine Content of the Brain

The values given in the literature for the ammonia content of the brain show wide variation (l-3). Most of these values are of doubtful reliability, since the methods of estimation have not generally taken into account the presence of labile acid amides such as glutamine, which are now known to occur in the brain and which easily liberate ammonia on treatment with alkalies under the conditions commonly used for the estimation of ammonia (4,5). Interest in the brain ammonia level centers around the fact that ammonia is a powerful cerebral irritant; the administration of ammonium salts causes convulsions and it has long been thought that ammonia may play a part in the precipitation of epileptic seizures (3-6). It would appear that the brain ammonia level is closely related to the glutamic acid-glutaminase system, which can remove ammonia by combination with glutamic acid to form glutamine (7). The report that glutamic acid inhibits ammonium chloride convulsions (8) may be significant in this connection, since it is known to reduce the incidence of attacks of petit ma1 in epileptics (9). The present paper reports an attempt to obtain reliable values for the ammonia content of rat brain with a method by which the free ammonia can be distinguished from the labile acid amide ammonia. At the same time a study has been made of the effect on the brain ammonia level of convulsant drugs and other factors which might affect it.