Excitatory amino acids: physiological and pharmacological probes for neuroscience research.

The 2S,3S,4S-isomer (L-CCG-I) of 2-(carboxycyclopropyl)glycine (CCG) is a potent metabotropic glutamate receptor agonist. L-CCG-I depressed monosynaptic excitation in the newborn rat spinal motoneurone at low concentrations well below those causing postsynaptic depolarization. 2S,3R,4S-CCG (L-CCG-IV) is a potent N-methyl-D-aspartate (NMDA)-type agonist. In cultured rat hippocampal neurones, L-CCG-IV caused marked increase in intracellular Ca2+ concentrations. 6-Carboxylated L-CCG-IV (DCG-IV), which is a tricarboxylated CCG derivative containing both chemical moieties of L-CCG-I and L-CCG-IV, depressed preferentially monosynaptic excitation of spinal reflexes in lower concentrations than L-CCG-I. 4-(2-Methoxyphenyl)-2-carboxy-3-pyrrolidineacetic acid (MFPA), which is the most potent kainoid yet described, is superior to acromelic acid A in causing depolarization of the newborn rat spinal motoneurone. In addition to MFPA, some non-kainoids demonstrated considerably high depolarizing activities. These new compounds would provide useful probes for neuroscience research.