Effect of Glutamic Acid on the Central Action of the Ammonium Ion

Abstract

In 1936, in a study of the effect of various stimulants and depressants of the central nervous system on the aftercontraction in humans, it was noted that small amounts of ammonium salts (.5 g ammonium), taken by mouth, caused a marked increase in this phenomenon. We have considered the aftercontraction a measure of the excitability of the human cerebral cortex., , It has been repeatedly affirmed in the literature that the concentration of ammonium ion increases in the brain tissue and cerebrospinal fluid in states of increased excitability of humans and animals. The fact that oral and parenteral administration of ammonium salts can produce convulsions in animals is well known. Since ammonium convulsions so closely simulate spontaneous seizures, it seemed that any substances which would prevent these seizures, might be useful in other types of convulsive activity. The work of Krebs on the metabolism of amino acids in brain tissue slices offered an important clue. Of many substances tested he found that glutamic acid specifically caused a marked reduction in the ammonium ion concentration present in the medium surrounding the tissue slices, due to the action of the enzyme glutaminase which synthesized glutamine from flutamic acid and ammonia.