title: Inhibition of uptake and release of a novel mGluR agonist (L-F2CCG-I) by anion transport blockers in the rat spinal cord.
abstract: A new metabotropic glutamate receptor (mGluR) agonist, (2S,1'S,2'S)-2-(2-carboxy-3,3-difluorocyclopropyl)glycine (L-F2CCG-I), induces a priming effect on (RS)-alpha-aminopimelate in the isolated spinal cord of newborn rats. Similar to (RS)-alpha-aminopimelate, L-glutamate (30-100 microM) neither affected spinal reflexes nor the resting membrane potentials of motoneurones, but preferentially potentiated the depression of monosynaptic excitation caused by L-F2CCG-I (0.4 microM). Following L-F2CCG-I treatment (1-2 microM), L-glutamate decreased the monosynaptic spinal reflexes in a concentration dependent manner, indicating a priming' effect of L-F2CCG-I. Thus L-glutamate is completely compatible with (RS)-alpha-aminopimelate in revealing the priming effect. An anion transport blocker, 4,4'-dinitrostilbene-2,2'-disulphonic acid (DNDS) (100 microM), markedly inhibited both the response to (RS)-alpha-aminopimelate and the induction of the L-F2CCG-I priming effect. The data suggest that L-F2CCG-I is Cl- -dependently incorporated into certain stores, and that (RS)-alpha-aminopimelate or L-glutamate must stimulate the release of L-F2CCG-I from the storage site. There were pharmacological similarities between the quisqualate and L-F2CCG-I priming effect. The physiological significance of the quisqualate or L-F2CCG-I priming is not yet established. L-F2CCG-I would be expected to be a useful pharmacological probe for elucidating the mechanism of the priming.
authors.affiliation: Department of Pharmacology, The Tokyo Metropolitan Institute of Medical Science, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ishida
authors.forename: H
authors.initials: H
authors.lastname: Shinozaki
mesh_terms: D000600:Amino Acids, Dicarboxylic / Q000493:pharmacokinetics*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000493:pharmacokinetics* / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D010867:Pimelic Acids / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013267:Stilbenes / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
chemical_list: C111411:2-(2-carboxy-3,3-difluorocyclopropyl)glycine; D000600:Amino Acids, Dicarboxylic; D018690:Excitatory Amino Acid Agonists; D010867:Pimelic Acids; D018094:Receptors, Metabotropic Glutamate; D013267:Stilbenes; C009845:alpha-aminopimelic acid; D018698:Glutamic Acid; C022306:4,4'-dinitro-2,2'-stilbenedisulfonic acid; D016318:Quisqualic Acid