Localization of metabotropic glutamate receptors 2/3 on primary afferent axons in the rat

Carlton, Susan M.; Hargett, Gregory L.; Coggeshall, Richard E.

doi:10.1016/s0306-4522(01)00238-x

Cited by 103 publications

(75 citation statements)

References 66 publications

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“…Group II mGluRs have been localized in dorsal root ganglion cells (Petralia et al, 1996) and on central processes of presumed primary afferent fibers (Jia et al, 1999). Our lab has localized Group II receptors on peripheral cutaneous processes and lumbar DRG cell bodies (Carlton et al, 2001b;Carlton and Hargett, 2007). Thus, it is highly likely that Group II mGluRs can modulate primary afferent mechanisms that lead to peripheral sensitization, as well as spinal mechanisms that lead to central sensitization.…”

Section: Localization Of Group II Mglurs On Peripheral Primary Afferentsmentioning

confidence: 98%

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

“…Approximately 40-50% of lumbar DRG cells express Group II mGluRs and these are mainly small to medium sized cells (mean diameter = 23μM) (Carlton et al, 2001b;Carlton and Hargett, 2007). The majority of DRG cells expressing Group II mGluRs (76%) stain positively for isolectin Griffonia Simplicifolia (I-B4) (Carlton et al, 2001b), suggesting that these cells either express low levels of peptides or they are non-peptidergic (Silverman and Kruger, 1990). Furthermore, 32% and 28% of unmyelinated and myelinated primary afferent axons, respectively, label for Group II mGluRs in the rat digital nerve (Carlton et al, 2001b), indicating that the receptors are transported out of the cell bodies to the peripheral terminals.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

“…We have reported the expression of Group II mGluRs on unmyelinated axons, many of which were presumed to be nociceptors, in the rat digital nerve (Carlton et al, 2001b). The goals of the present study are to further our understanding of Group II modulation of nociceptor processing in the periphery, documenting behavioral changes using inflammatory models and documenting, for the first time, cutaneous single fiber activity following exposure to a Group II agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) and antagonist LY341495 (LY).…”

Section: Introductionmentioning

confidence: 99%

“…The majority of DRG cells expressing Group II mGluRs (76%) stain positively for isolectin Griffonia Simplicifolia (I-B4) (Carlton et al, 2001b), suggesting that these cells either express low levels of peptides or they are non-peptidergic (Silverman and Kruger, 1990). Furthermore, 32% and 28% of unmyelinated and myelinated primary afferent axons, respectively, label for Group II mGluRs in the rat digital nerve (Carlton et al, 2001b), indicating that the receptors are transported out of the cell bodies to the peripheral terminals. Consistent with this anatomical localization, intraplantar injection of a Group II agonist blocks prostaglandin E 2 -induced thermal (Yang and Gereau, 2002) and mechanical (Yang and Gereau, 2003) sensitization in mice.…”

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Group II metabotropic glutamate receptor activation attenuates peripheral sensitization in inflammatory states

Zhou

Carlton

2008

Neuroscience

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Several lines of evidence indicate that Group II metabotropic glutamate receptor (mGluR) activation can depress sensory transmission. We have reported the expression of Group II mGluRs on unmyelinated axons, many of which were presumed to be nociceptors, in the rat digital nerve (Carlton et al., 2001b). The goals of the present study are to further our understanding of Group II modulation of nociceptor processing in the periphery, documenting behavioral changes using inflammatory models and documenting, for the first time, cutaneous single fiber activity following exposure to a Group II agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) and antagonist LY341495 (LY). The data indicate that peripheral Group II mGluR activation does not depress nociceptive behaviors or nociceptor fiber responses in the non-sensitized state (i.e. following brief nociceptive mechanical or thermal stimulation) but can depress these responses when nociceptors are sensitized by exposure to formalin or inflammatory soup. Group II mGluR agonist-induced inhibition can be blocked by a selective Group II antagonist. Peripheral Group II mGluR-induced inhibition evoked in these studies occurs through activation of local receptors and not through spinal or supraspinal mechanisms. The data indicate that administration of selective Group II agonists may be potent therapeutic agents for prevention of peripheral sensitization and for treatment of inflammatory pain. KeywordsGroup II mGluR; pain; APDC; LY341495; formalin; inflammation; inflammatory soup Glutamate and glutamate receptors play an important role in peripheral pain mechanisms in animals (Carlton, 2001;Carlton et al., 2003) and humans (McNearney et al., 1999;McNearney et al., 2000;Cairns et al., 2001;Alfredson et al., 2001;Alfredson and Lorentzon, 2002;Svensson et al., 2003;Cairns et al., 2003). To date, ionotropic glutamate receptors (iGluRs) including N-methyl-D-aspartate (NMDA) and non-NMDA receptors are implicated in peripheral cutaneous pain mechanisms Bleakman et al., 2006).More recent studies indicate that metabotropic glutamate receptors (mGluRs) can modulate peripheral nociceptor function. In contrast to iGluRs, which are ligand-gated ion channel receptors, mGluRs mediate their function via G-protein coupled receptors which trigger Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2009 June 23. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript intracellular second-messenger systems (Pin and Duvoisin, 1995). Accordin...

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Section: Localization Of Group II Mglurs On Peripheral Primary Afferentsmentioning

confidence: 98%

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Group II metabotropic glutamate receptor activation attenuates peripheral sensitization in inflammatory states

Zhou

Carlton

2008

Neuroscience

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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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Colocalization of metabotropic glutamate receptors in rat dorsal root ganglion cells

Carlton

Hargett

2007

J of Comparative Neurology

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Glutamate is the main excitatory transmitter in both central and peripheral nervous systems. Discovery of metabotropic glutamate receptors (mGluRs) made it clear that glutamate can have excitatory or inhibitory effects on neuronal function, with group I mGluRs enhancing cell excitability but group II and III mGluRs decreasing excitability. The present study investigated the colocalization of mGluR subtypes representing groups I, II, or III in rat L5 dorsal root ganglion (DRG) cells. The analyses show that group III has the highest expression, with 75.0% of DRG cells expressing mGluR8, followed by group II, with 51.6% expressing mGluR2/3, followed by group I, with only 6.8% expressing mGluR1alpha. mGluR8 is expressed by small, medium, and large diameter cells. In contrast, mGluR1alpha and mGluR2/3 are expressed by mainly small and medium cells. Approximately half of cells expressing group I mGluR1alpha also express either group II mGluR2/3 or group III mGluR8. These mGluR1alpha double-labeled populations are not likely to overlap since >1.0% of mGluR1alpha are triple-labeled. As expected from the high percentage of single-labeled mGluR2/3 and mGluR8 cells, there is a considerable population of double-labeled cells with approximately 30% of each population expressing both receptors. Due to the fact that the number of mGluR1alpha-expressing cells in the DRG is low, the percentage of triple-labeled cells is also low ( approximately 1-2%). The prevalence of groups II and III indicate that glutamate could have a substantial inhibitory effect of primary afferent function, reducing and/or fine-tuning sensory input before transmission to the spinal cord. These anatomical data highlight the potential inhibitory role glutamate may play in peripheral sensory transmission.

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Localization of metabotropic glutamate receptors 2/3 on primary afferent axons in the rat

Cited by 103 publications

References 66 publications

Group II metabotropic glutamate receptor activation attenuates peripheral sensitization in inflammatory states

Group II metabotropic glutamate receptor activation attenuates peripheral sensitization in inflammatory states

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

Colocalization of metabotropic glutamate receptors in rat dorsal root ganglion cells

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