L-beta-methylaminoalanine inhibits [3H]glutamate binding in the presence of bicarbonate ions.

We examined the ability of the neurotoxin, L-beta-methylaminoalanine (L-BMAA), to inhibit [3H]glutamate binding to rat brain synaptic junctions. In a tris(hydroxymethyl)aminomethane acetate buffer, L-BMAA did not affect [3H]glutamate binding (IC50 greater than 10 mM). However, in the presence of ammonium bicarbonate (20 mM) L-BMAA blocked [3H]glutamate binding with an IC50 of 1 mM. This inhibition was not caused by ammonium ion since other ammonium salts were inactive. Furthermore, identical inhibition was obtained in the presence of potassium bicarbonate. Bicarbonate ion did not alter the ability of N-methyl-D-aspartic acid to block glutamate binding. These results indicate that bicarbonate ion is required for the interaction of L-BMAA with the glutamate receptor and may account for the observation that beta-methylaminoalanine is neurotoxic in vitro only in the presence of bicarbonate.