A metabotropic L-glutamate receptor agonist: pharmacological difference between rat central neurones and crayfish neuromuscular junctions.
1. 2S,3S,4S-2-(carboxycyclopropyl)glycine (L-CCG-I), a conformationally restricted glutamate analogue, is a potent metabotropic L-glutamate receptor agonist in the mammalian central nervous system. 2. Depolarizing actions of L-CCG-I and trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD) in the newborn rat spinal motoneurone are temperature-sensitive, and are not depressed by 3-[(+/-)-2-carboxypiperazin-4-yl] propyl-1-phosphonic acid (CPP) and/or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). 3. L-CCG-I and trans-ACPD induced oscillatory responses in Xenopus oocytes injected with rat brain mRNA. Oocytes with oscillatory responses to L-CCG-I and trans-ACPD showed reversal potential of about -20 mV, which was very close to the equilibrium potential of chloride ions. 4. In rat hippocampal synaptoneurosomes, L-CCG-I stimulated phosphoinositide hydrolysis in a concentration dependent manner. L-CCG-I was less potent than quisqualate but more potent than trans-ACPD. 5. At low concentrations, L-CCG-I did not cause any depolarization of newborn rat spinal motoneurones, but reduced substantially amplitudes of monosynaptic reflexes. 6. At the crayfish neuromuscular junction L-CCG-I, acting presynaptically, reduced the amplitude of excitatory junctional potentials. This action was prevented by application of picrotoxin but not pertussis toxin. The actions of trans-ACPD differ from those of either L-CCG-I or ibotenate at the crayfish neuromuscular junction. 7. L-CCG-I has a potential to provide further useful information on metabotropic L-glutamate receptor function.
Tokyo Metropolitan Institute of Medical Science, Japan.
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Shinozaki
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Ishida
D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology*; D000818:Animals; D003400:Astacoidea; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000502:physiology; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
D000600:Amino Acids, Dicarboxylic; D010716:Phosphatidylinositols; D017470:Receptors, Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C035261:(alpha-carboxycyclopropyl)glycine