Gamma-L-glutamyl-L-glutamate is an endogenous dipeptide in the rat olfactory bulb which activates N-methyl-D-aspartate receptors.

The concentration of gamma-L-glutamyl-L-glutamate (gamma-glu-glu), a potent displacer of excitatory amino acid receptor binding, and other structurally related dipeptides were determined in extracts of the rat olfactory bulb by a novel liquid chromatographic method. Whole-cell patch clamp recordings of currents from freshly isolated neurons showed that gamma-glu-glu produced inward currents at negative holding potentials, provided microM concentrations of glycine were added and no Mg(2+)-ions were present, indicating activation of N-methyl-D-aspartate receptors. Consistently, geometry optimization of gamma-glu-glu using molecular mechanics calculations, suggested a bent conformer with structural features supporting this view.