Group II and group III metabotropic glutamate receptor agonists depress synaptic transmission in the rat spinal cord dorsal horn

Gerber, Gábor; Zhong, Jingquan; Youn, Dong‐ho; Randić, Mirjana

doi:10.1016/s0306-4522(00)00269-4

Cited by 104 publications

(79 citation statements)

References 101 publications

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“…Activation of group II and III mGluRs also inhibits glutamatergic transmission in many brain regions and in the normal spinal cord (Jane et al, 1996;Conn and Pin, 1997;Gerber et al, 2000). Activation of group II and III mGluRs attenuates the firing activity of spinal dorsal horn neurons in acute and chronic pain models (Neugebauer et al, 2000;Chen and Pan, 2005).…”

Section: Effect Of Group II and Iii Metabotropic Glutamate Receptor Amentioning

confidence: 99%

“…Activation of group II and III mGluRs attenuates the firing activity of spinal dorsal horn neurons in acute and chronic pain models (Neugebauer et al, 2000;Chen and Pan, 2005). Some group II and III mGluRs are also localized on the GABAergic interneurons and terminals in the spinal cord (Jia et al, 1999), and group II and III mGluR agonists decrease synaptic GABA release in normal spinal cord slices (Gerber et al, 2000). Notably, it is the integration of excitatory and inhibitory inputs that shapes the output of nociceptive signals in the spinal dorsal horn.…”

Section: Effect Of Group II and Iii Metabotropic Glutamate Receptor Amentioning

confidence: 99%

“…The signaling mechanisms responsible for the inhibitory effect of presynaptic group II and III mGluRs on synaptic transmission in the spinal cord are not known at present. In addition to exerting an inhibitory effect on glutamate release from the primary afferents (Gerber et al, 2000), group II and III mGluRs play an important role in the regulation of GABAergic synaptic transmission in the spinal cord when the nociceptive primary afferents are stimulated with capsaicin (Zhou et al, 2007). In about 50% of lamina II neurons, increased nociceptive inflow reduces synaptic GABA release through activation of presynaptic group II and III mGluRs in spinal cord slices (Zhou et al, 2007).…”

Section: Effect Of Group II and Iii Metabotropic Glutamate Receptor Amentioning

confidence: 99%

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Modulation of pain transmission by G-protein-coupled receptors

Pan

Zhou

et al. 2008

Pharmacology & Therapeutics

169

116

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The heterotrimeric G protein-coupled receptors (GPCRs) represent the largest and most diverse family of cell surface receptors and proteins. GPCRs are widely distributed in the peripheral and central nervous systems and are one of the most important therapeutic targets in pain medicine. GPCRs are present on the plasma membrane of neurons and their terminals along the nociceptive pathways and are closely associated with the modulation of pain transmission. GPCRs that can produce analgesia upon activation include opioid, cannabinoid, α 2 -adrenergic, muscarinic acetylcholine, γ-aminobutyric acid B (GABA B ), group II and III metabotropic glutamate, and somatostatin receptors. Recent studies have led to a better understanding of the role of these GPCRs in the regulation of pain transmission. Here, we review the current knowledge about the cellular and molecular mechanisms that underlie the analgesic actions of GPCR agonists, with a focus on their effects on ion channels expressed on nociceptive sensory neurons and on synaptic transmission at the spinal cord level.

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Section: Effect Of Group II and Iii Metabotropic Glutamate Receptor Amentioning

confidence: 99%

Section: Effect Of Group II and Iii Metabotropic Glutamate Receptor Amentioning

confidence: 99%

Section: Effect Of Group II and Iii Metabotropic Glutamate Receptor Amentioning

confidence: 99%

See 1 more Smart Citation

Modulation of pain transmission by G-protein-coupled receptors

Pan

Zhou

et al. 2008

Pharmacology & Therapeutics

169

116

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“…The mGluRs have complex and diverse actions in the central nervous system, and activation of mGluRs in the spinal cord may produce facilitatory or inhibitory effects (Budai and Larson, 1998;Gerber et al, 2000). Electrophysiological and behavioral studies have shown that group I mGluRs are involved in persistent and enhanced nociception (Young et al, 1994;Fisher and Coderre, 1996;Young et al, 1997;Budai and Larson, 1998).…”

mentioning

confidence: 99%

“…Electrophysiological and behavioral studies have shown that group I mGluRs are involved in persistent and enhanced nociception (Young et al, 1994;Fisher and Coderre, 1996;Young et al, 1997;Budai and Larson, 1998). Activation of groups II and III mGluRs has been shown to inhibit synaptic transmission in many brain regions as well as in the spinal cord in vitro (Baskys and Malenka, 1991;Jane et al, 1996;Conn and Pin, 1997;Gerber et al, 2000). The role of groups II and III mGluRs in the modulation of spinal nociceptive processing is less clear.…”

mentioning

confidence: 99%

Distinct Roles of Group III Metabotropic Glutamate Receptors in Control of Nociception and Dorsal Horn Neurons in Normal and Nerve-Injured Rats

Chen

Pan²

2004

J Pharmacol Exp Ther

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Increased glutamatergic input to spinal dorsal horn neurons constitutes an important mechanism for neuropathic pain. However, the role of group III metabotropic glutamate receptors (mGluRs) in regulation of nociception and dorsal horn neurons in normal and neuropathic pain conditions is not fully known. In this study, we determined the effect of the group III mGluR specific agonist L(ϩ)-2-amino-4-phosphonobutyric acid (L-AP4) on nociception and dorsal horn projection neurons in normal rats and a rat model of neuropathic pain. Tactile allodynia was induced by ligation of L5/L6 left spinal nerves in rats. Allodynia was determined by von Frey filaments in nerve-injured rats. The nociceptive threshold was tested using a radiant heat and a Randall-Selitto pressure device in normal rats. Single-unit activity of ascending dorsal horn neurons was recorded from the lumbar spinal cord in anesthetized rats. An intrathecal (5-30 g) L-AP4 dose-dependently attenuated allodynia in nerve-injured rats but had no antinociceptive effect in normal rats. Topical spinal application of 5 to 50 M L-AP4 also significantly inhibited the evoked responses of ascending dorsal horn neurons in nerve-ligated but not normal rats. Furthermore, blockade of spinal group III mGluRs significantly decreased the withdrawal threshold and increased the evoked responses of dorsal horn neurons in normal but not nerve-injured rats. These data suggest that group III mGluRs play distinct roles in regulation of nociception and dorsal horn neurons in normal and neuropathic pain states. Activation of spinal group III mGluRs suppresses allodynia and inhibits the hypersensitivity of dorsal horn projection neurons associated with neuropathic pain.

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Characterization of phosphoproteins from electrophoretic gels by nanoscale Fe(III) affinity chromatography with off-line mass spectrometry analysis

2001

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Detailed characterization of phosphoproteins as well as other post-translationally modified proteins is required to fully understand protein function and regulatory events in cells and organisms. Here we present a mass spectrometry (MS) based experimental strategy for the identification and mapping of phosphorylation site(s) using only low-picomole amounts of phosphoprotein starting material. Miniaturized sample preparation methods for MS facilitated localization of phosphorylation sites in phosphoproteins isolated by polyacrylamide gel electrophoresis. Custom made, nanoscale immobilized Fe(III) affinity chromatography (Fe(III)-IMAC) columns were employed for enrichment of phosphorylated peptides from crude peptide mixtures prior to off-line analysis by matrix-assisted laser desorption/ionization (MALDI) MS or nanoelectrospray tandem mass spectrometry (MS/MS). An optimized and sensitive procedure for alkaline phosphatase treatment of peptide mixtures was implemented, which in combination with nano-scale Fe(III)-IMAC and MALDI-MS allowed unambiguous identification of phosphopeptides by observation of 80 Da mass shifts. Nanoelectrospray MS/MS was used for phosphopeptide sequencing for exact determination of phosphorylation sites. The advantages and limitations of the experimental strategy was demonstrated by enrichment, identification and sequencing of phosphopeptides from the model proteins ovalbumin and bovine beta-casein isolated by gel electrophoresis. Furthermore, an autophosphorylation site at Ser-3 in recombinant human casein kinase-2 beta subunit was determined. The potential of miniaturized Fe(III)-IMAC and MALDI-MS for characterization of in vivo phosphorylated proteins was demonstrated by identification of tryptic phosphopeptides derived from the human p47/phox phosphoprotein isolated by two-dimensional gel electrophoresis.

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Group II and group III metabotropic glutamate receptor agonists depress synaptic transmission in the rat spinal cord dorsal horn

Cited by 104 publications

References 101 publications

Modulation of pain transmission by G-protein-coupled receptors

Modulation of pain transmission by G-protein-coupled receptors

Distinct Roles of Group III Metabotropic Glutamate Receptors in Control of Nociception and Dorsal Horn Neurons in Normal and Nerve-Injured Rats

Characterization of phosphoproteins from electrophoretic gels by nanoscale Fe(III) affinity chromatography with off-line mass spectrometry analysis

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