(2 S,1′ R,2′ R,3′ R)-2-(2,3-dicarboxycyclopropyl) glycine positively modulates metabotropic glutamate receptors coupled to polyphosphoinositide hydrolysis in rat hippocampal slices

doi:10.1016/0006-8993(94)90857-5

Brain Research

Volume 659, Issues 1–2, 3 October 1994, Pages 10-16

https://doi.org/10.1016/0006-8993(94)90857-5 Get rights and content

Abstract

In rat hippocampal slices, the novel metabotropic glutamate receptor (mGluR) ligand, (1 _S,1′ _R,2′ _R,3′ _R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) enhanced the stimulation of polyphosphoinositide (PPI) hydrolysis elicited by quisqualate or by submaximal concentrations of ibotenate or (1 _S,3 _R)-1aminocyclopentane-1,3-dicarboxylic acid (1 _S,3 _R-ACPD). The enhancing effect of DCG-IV was (i) specific for mGluR agonists, (ii) restricted to hippocampal slice preparation, (iii) reversible, and (iv) not subject to homologous desensitization. In addition, DGC-IV did not interact with l-2-amino-4-phosphonobutanoate (AP4), a noncompetitive antagonist of mGluRs coupled to PPI hydrolysis in brain slices [32]. The action of DCG-IV on quisqualate-stimulated PPI hydrolysis was insensitive to antagonists of ionotropic glutamate receptors and did not appear to be a consequence of a reduction in the intracellular levels of cAMP [14]. When the stimulation of PPI hydrolysis was measured as a function of the incubation time, DCG-IV potentiated quisqualate-stimulated PPI hydrolysis after 60 min of incubation, when quisqualate had already reached its maximal effect. Knowing that activation of protein kinase C (PKC) limits the extent of mGluR agonist-stimulated PPI hydrolysis over time, we have studied the enhancing effect of DCG-IV in the presence of the PKC activator, 12-O-tetradecanoylphorbol-13-acetate (TPA). As expected [9], TPA reduced quisqualate-stimulated PPI hydrolysis in control slices, but was inactive in slices incubated in the presence of DCG-IV. Taken collectively, these results suggest that DCG-IV positively modulates the activity of mGluRs coupled to PPI hydrolysis through a mechanism, which involves PKC-mediated phosphorylation processes.

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(2 S,1′ R,2′ R,3′ R)-2-(2,3-dicarboxycyclopropyl) glycine positively modulates metabotropic glutamate receptors coupled to polyphosphoinositide hydrolysis in rat hippocampal slices

Abstract

Neuron

Trends Neurosci.

Trends Pharmacol. Sci.

J. Biol. Chem.

Brain Res.

Brain Res.

Eur. J. Pharmacol. (Mol. Pharmacol. Sect.)

Bioorg. Med. Chem. Lett.

Eur. J. Pharmacol.

Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca 2+ signal transduction

J. Biol. Chem.

Protein kinase C and long-term potentiation in the hippocampus

Trends Pharmacol. Sci.

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J. Neurochem.

Glutamate and quisqualate regulate expression of metabotropic glutamate receptor mRNA in cultured cerebellar granule cells

J. Neurochem.

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Phorbol esters attenuate glutamate-stimulated inositol-phospholipid hydrolysis in neuronal cultures

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J. Neurochem.

Pharmacology and physiology of metabotropic glutamate receptors in mammalian central nervous system

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(2 _S,1′ _R,2′ _R,3′ _R)-2-(2,3-dicarboxycyclopropyl) glycine positively modulates metabotropic glutamate receptors coupled to polyphosphoinositide hydrolysis in rat hippocampal slices

Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca ²⁺ signal transduction