![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
C Thomsen, V Bruno, F Nicoletti, M Marinozzi and R Pellicciari
Department of Molecular Pharmacology, Novo Nordisk A/S, Malov, Denmark. cht@novo.dk
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 (KB = 8.2 +/- 0.4 microM). 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 alpha-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 microM), whereas a higher dose of PCCG-IV (80 microM) was similarly neuroprotective to L-2-amino-4-phosphonobutanoate. The neuroprotective effect of PCCG-IV was blocked by an antagonist of mGluR4a, alpha-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.
This article has been cited by other articles:
|
|
 |
|
  C. Corti, G. Battaglia, G. Molinaro, B. Riozzi, A. Pittaluga, M. Corsi, M. Mugnaini, F. Nicoletti, and V. Bruno The Use of Knock-Out Mice Unravels Distinct Roles for mGlu2 and mGlu3 Metabotropic Glutamate Receptors in Mechanisms of Neurodegeneration/Neuroprotection J. Neurosci., August 1, 2007; 27(31): 8297 - 8308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Albani-Torregrossa, S. Attucci, M. Marinozzi, R. Pellicciari, F. Moroni, and D. E. Pellegrini-Giampietro Antagonist Pharmacology of Metabotropic Glutamate Receptors Coupled to Phospholipase D Activation in Adult Rat Hippocampus: Focus on (2R,1'S,2'R,3'S)-2-(2'-Carboxy-3'-phenylcyclopropyl)glycine Versus 3,5-Dihydroxyphenylglycine Mol. Pharmacol., April 1, 1999; 55(4): 699 - 707. [Abstract] [Full Text]
|
|
|
|
 |
|
 N. A. Breakwell, M. J. Rowan, and R. Anwyl (+)-MCPG Blocks Induction of LTP in CA1 of Rat Hippocampus via Agonist Action at an mGluR Group II Receptor J Neurophysiol, March 1, 1998; 79(3): 1270 - 1276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Bruno, F. X. Sureda, M. Storto, G. Casabona, A. Caruso, T. Knopfel, R. Kuhn, and F. Nicoletti The Neuroprotective Activity of Group-II Metabotropic Glutamate Receptors Requires New Protein Synthesis and Involves a Glial-Neuronal Signaling J. Neurosci., March 15, 1997; 17(6): 1891 - 1897. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
