(2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine, a potent and selective antagonist of type 2 metabotropic glutamate receptors

Christian Thomsen, Valeria Bruno, Ferdinando Nicoletti, Maura Marinozzi, Roberto Pellicciari

Research output: Contribution to journalArticlepeer-review

Abstract

The pharmacological profile of (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'- phenylcyclopropyl)glycine (PCCG-IV) at metabotropic glutamate receptor (mGluR) subtypes mGluR1a, mGluR2, mGluR4a, and mGluR5 was examined. PCCG-IV potently antagonized glutamate-induced inhibition of forskolin-stimulated cAMP formation in baby hamster kidney cells expressing mGluR2 in a competitive manner (K(B) = 8.2 ± 0.4 μM). PCCG-IV was a weak agonist at mGluR4a but inactive at the cloned phosphoinositide-coupled mGluRs (mGluR1a and mGluR5a). PCCG-IV was significantly more potent and selective as an antagonist at mGluR2 compared with previously described mGluR2 antagonists, including α-methyl-4-carboxyphenylglycine. In mice cortical neurons, PCCG- IV antagonized the neuroprotective effects of a selective mGluR2 agonist, (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine, at low doses (0.2-20 μM), whereas a higher dose of PCCG-IV (80 μM) was similarly neuroprotective to L-2-amino-4-phosphonobutanoate. The neuroprotective effect of PCCG-IV was blocked by an antagonist of mGluR4a, α-methyl-4-phosphonophenylglycine. Thus, PCCG-IV is a novel and useful tool for delineating the physiological roles of group II mGluRs in the central nervous system.

Original languageEnglish
Pages (from-to)6-9
Number of pages4
JournalMolecular Pharmacology
Volume50
Issue number1
Publication statusPublished - Jul 1996

ASJC Scopus subject areas

  • Pharmacology

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