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 p otent displacer of excitatory amino acid receptor binding, and other s tructurally related dipeptides were determined in extracts of the rat olfactory bulb by a novel liquid chromatographic method. Whole-cell pa tch clamp recordings of currents from freshly isolated neurons showed that gamma-glu-glu produced inward currents at negative holding potent ials, provided muM concentrations of glycine were added and no Mg2+-io ns were present, indicating activation of N-methyl-D-aspartate recepto rs. Consistently, geometry optimization of gamma-glu-glu using molecul ar mechanics calculations, suggested a bent conformer with structural features supporting this view.