A SIGNIFICANT INCREASE IN INTRACELLULAR CA2+ CONCENTRATION INDUCED BY (2S,3R,4S)-2-(CARBOXYCYCLOPROPYL)GLYCINE, A NEW POTENT NMDA AGONIST, IN CULTURED RAT HIPPOCAMPAL-NEURONS

The increase in intracellular Ca2+ concentration, [Ca2+]i, induced by isomers of 2-(carboxycyclopropyl)glycine (CCG) was examined in cultured rat hippocampal neurons. Some CCG isomers and N-methyl-D-aspartate (NMDA) increased [Ca2+]i in a concentration dependent manner. The 2S,3R,4S isomer of CCG (L-CCG-IV) was the most potent in elevating [Ca2+]i, and its activity was more than 100 times higher than that of NMDA and about 10 times higher than that of L-glutamate. The increase in [Ca2+]i was effectively blocked by NMDA blockers and Mg2+, and was markedly augmented by the addition of a low concentration of glycine. L-CCG-IV would be a useful tool for elucidation of functions of NMDA receptors.