A novel metabotropic glutamate receptor agonist: marked depression of monosynaptic excitation in the newborn rat isolated spinal cord.
1. Neuropharmacological actions of a novel metabotropic glutamate receptor agonist, (2S,1'R,2'R,3'R)-2(2,3-dicarboxycyclopropyl)glycine (DCG-IV), were examined in the isolated spinal cord of the newborn rat, and compared with those of the established agonists of (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I) or (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD). 2. At concentrations higher than 10 microM, DCG-IV caused a depolarization which was completely blocked by selective N-methyl-D-aspartate (NMDA) antagonists. The depolarization was pharmacologically quite different from that caused by L-CCG-I and (1S,3R)-ACPD. 3. DCG-IV reduced the monosynaptic excitation of motoneurones rather than polysynaptic discharges in the nanomolar range without causing postsynaptic depolarization of motoneurones. DCG-IV was more effective than L-CCG-I, (1S,3R)-ACPD or L-2-amino-4-phosphonobutanoic acid (L-AP4) in reducing the monosynaptic excitation of motoneurones. 4. DCG-IV (30 nM-1 microM) did not depress the depolarization induced by known excitatory amino acids in the newborn rat motoneurones, but depressed the baseline fluctuation of the potential derived from ventral roots. Therefore, DCG-IV seems to reduce preferentially transmitter release from primary afferent nerve terminals. 5. Depression of monosynaptic excitation caused by DCG-IV was not affected by any known pharmacological agents, including 2-amino-3-phosphonopropanoic acid (AP3), diazepam, 2-hydroxysaclofen, picrotoxin and strychnine. 6. DCG-IV has the potential of providing further useful information on the physiological function of metabotropic glutamate receptors.
Ishida
M
M
Tokyo Metropolitan Institute of Medical Science, Japan.
Saitoh
T
T
Shimamoto
K
K
Ohfune
Y
Y
Shinozaki
H
H
D000596:Amino Acids / Q000494:pharmacology; D000600:Amino Acids, Dicarboxylic / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003521:Cyclopropanes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004558:Electric Stimulation; D004594:Electrophysiology; D005998:Glycine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D012023:Reflex, Monosynaptic / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*
D000596:Amino Acids; D000600:Amino Acids, Dicarboxylic; D003521:Cyclopropanes; D009467:Neuromuscular Depolarizing Agents; D009498:Neurotoxins; D017470:Receptors, Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C082313:2-(2,3-dicarboxycyclopropyl)glycine; C035261:(alpha-carboxycyclopropyl)glycine; D016202:N-Methylaspartate; D005998:Glycine