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A novel metabotropic glutamate receptor agonist: marked depression of monosynaptic excitation in the newborn rat isolated spinal cord
Author(s) -
Ishida M.,
Saitoh T.,
Shimamoto K.,
Ohfune Y.,
Shinozaki H.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13745.x
Subject(s) - acpd , depolarization , metabotropic receptor , metabotropic glutamate receptor , quisqualic acid , chemistry , excitatory postsynaptic potential , glutamate receptor , nmda receptor , agonist , neuroscience , strychnine , biophysics , pharmacology , receptor , kainic acid , biology , biochemistry
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,3 R )‐1‐aminocyclopentane‐1,3‐dicarboxylic acid ((1S,3 R )‐ACPD). 2 At concentrations higher than 10 μ m , 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,3 R )‐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,3 R )‐ACPD or l ‐2‐amino‐4‐phosphonobutanoic acid ( l ‐AP4) in reducing the monosynaptic excitation of motoneurones. 4 DCG‐IV (30 n m –1 μ m ) 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.