Abstract: In tests on neurones in the cat spinal cord in vivo, and frog and immature rat spinal cord in vitro, cis-2,3-piperidine dicarboxylate (cis-2,3-PDA) produced the following effects: (1) selective antagonism of amino acid-induced responses, compared with responses to other putative transmitters; (2) effective antagonism of kainate and quisqualate-induced responses in addition to responses induced by N-methyl-D-aspartate (NMDA) and other excitatory amino acids; (3) partial NMDA-like agonist action; (4) antagonism of dorsal root-evoked excitation of Renshaw cells; (5) potentiation of acetylcholine- and ventral root-evoked excitation of Renshaw cells. This unique spectrum of action may be useful for transmitter receptor characterization in the vertebrate central nervous system.

Abstract: The aim of the present paper was to determine whether the release of glutamate from putative "glutamergic" terminals in the cerebellum is influenced by gamma-aminobutyric acid (GABA). In a group of preliminary experiments, we present biochemical evidence in favour of a neurotransmitter role of glutamate in the cerebellum: (1) endogenous glutamate was released from depolarized cerebellar synaptosomal preparations in a Ca2+-dependent away; (2) [14C]glutamate was synthesized from [14C]glutamine in cerebellar synaptosomes, and the newly synthesized [14C]glutamate was released released in a Ca2+-dependent way; (3) the elevation of cyclic GMP elicited by depolarization of cerebellar slices in the presence of Ca2+ was partly reversed by the glutamate antagonist glutamic acid diethyl ester, which probably prevented the interaction of endogenously released glutamate with postsynaptic receptors. GABA and muscimol at low concentrations (2--20 micrometers) potentiated the depolarization-induced release of D-[3H]aspartate (a glutamate analogue which labels the glutamate "reuptake pool") from cerebellar synaptosomes. The effect was concentration dependent and was largely prevented by two GABA antagonists, bicuculline and picrotoxin. The stimulation of D-[3H]aspartate release evoked by muscimol was linearly related to the logarithm of K+ concentration in the depolarizing medium. GABA did not affect the overall release of endogenous glutamate, but potentiated, in a picrotoxin-sensitive manner, the depolarization-evoked release of [14C]glutamate previously synthesized from [14C]glutamine. Since nerve endings are the major site of glutamate synthesis from glutamine, GABA and muscimol appear to exert their stimulatory effect at the level of "glutamergic" nerve terminals, probably after interacting with presynaptic GABA receptors. The possible functional significance of these findings is briefly discussed.

Abstract: The influence of 1 mm-l-proline on electrically stimulated release of endogenous glutamate from slices of rat frontal cortex was measured. One mm-l-proline approximates the in vitro concentration that inhibits glutamate-induced spreading depression. Also, this l-proline level has been reported to be present in brain after an intraperitoneal injection that induced amnesia in chicks. l-Proline but not d-proline exhibits an inhibitory effect on glutamate release, thus supporting the suggestion that this mechanism may play a role in memory retention and/or formation.

Abstract: The studies described above have provided evidence for the presence of a high affinity, glutamate binding glycoprotein which has some of the pharmacologic characteristics of the recognition site of neuronal glutamate receptors. In addition, evidence was presented for the distinct molecular nature of this glutamate binding protein as compared to that of the kainic acid binding macromolecule in synaptic membranes and also, for the differential characteristics of the glutamate binding sites as compared to the glutamate transport carriers. Finally, information was presented which is suggestive of the presence and functional integrity of glutamate receptor.ion channel complexes in synaptic membrane preparations.