Actions of D and L forms of 2-amino-5-phosphonovalerate and 2-amino-4-phosphonobutyrate in the cat spinal cord.
The separate optical enantiomers of 2-amino-5-phosphonovalerate (APV) and 2-amino-4-phosphonobutyrate (APB) have been tested for their ability to modify amino acid-induced and synaptic excitation of cat spinal neurones. D-(-)-APV was a highly potent and selective antagonist of amino acid-induced and synaptic excitation. Polysynaptic excitation was more susceptible to antagonism by D-APV than was monosynaptic excitation. It was considered likely that the depression of synaptic excitation by D-APV was due to the blockade of an excitatory amino acid transmitter acting at N-methyl-D-aspartate (NMDA) receptors. L-(+)-APV showed a relatively weak amino acid and synaptic blocking activity, which was similar in character to that of D-APV, and which may have been due to a slight residuum of the D isomer in the sample of the L form used. D-(-)-APB was a weak and relatively non-selective antagonist of amino acid-induced responses. In contrast, L-(+)-APB either had no effect or, at higher concentrations, enhanced these responses. Both isomers depressed synaptic responses in a proportion of the cells tested, the L form being the more potent isomer in producing this effect. Monosynaptic and polysynaptic excitations were both susceptible to this type of action. The depression of synaptic excitation by D-APB may have been due in some cases to the blockade of an excitatory amino acid transmitter. However, it is unlikely that the synaptic depressant action of L-APB is due to this mechanism.
D015763:2-Amino-5-phosphonovalerate; D000613:Aminobutyrates / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D003864:Depression, Chemical; D007395:Interneurons / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors; D013116:Spinal Cord / Q000187:drug effects*; D013237:Stereoisomerism; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000613:Aminobutyrates; D018377:Neurotransmitter Agents; D015763:2-Amino-5-phosphonovalerate; C012729:2-amino-4-phosphonobutyric acid; D014633:Valine