Characterization of group Ⅰ metabotropic glutamate receptors in rat superior cervical ganglion and their changes following chronic intermittent hypoxia / 解剖学报

Objective To observe the expression and localization of group Ⅰ metabotropic glutamate receptors (mGluR1/ 5) in rat superior cervical ganglion (SCG) and the effect of chronic intermittent hypoxia (CIH) on mGluR1/ 5 protein level. Methods Twelve male SD rats were randomly divided into control group(Ctrl)and CIH group(CIH), 6 rats in each group. After 6 weeks of modeling, the effect of CIH on mGluR1/ 5 protein level was detected by Western blotting, the expression and distribution of mGluR1/ 5 in SCG were detected by immunohistochemistry and double-immunofluorescent staining. Results mGluR1/ 5 was expressed in rat SCG. mGluR1 was distributed in neurons and small intensely fluorescent (SIF) cells, but not in satellite glial cells (SGCs), nerve fibers and blood vessels, whereas mGluR5 was mainly distributed in nerve fibers and a little in neurons, but not in SGCs, SIF cells and blood vessels. CIH increased the protein levels of mGluR1/ 5 (P<0. 01) in rat SCG. Conclusion Both mGluR1 and mGluR5 are expressed in the rat SCG, but their distribution are different, and the increased protein levels of both may be involved in CIH-induced hypertension.

Role of Homer1a/mGluR5 signaling pathway in cognitive dysfunction induced by sleep deprivation in aged rats / 中华麻醉学杂志

Objective:To evaluate the role of Homer1a/metabotropic glutamate receptor 5 (mGluR5) signaling pathway in sleep deprivation-induced cognitive dysfunction in aged rats.Methods:One hundred and four SPF healthy male Sprague-Dawley rats, aged 22-24 months, weighing 320-360 g, were divided into 4 groups ( n=26 each) using a random number table method: normal control group (group Control), sleep deprivation+ vehicle group (group SD+ Vehicle), sleep deprivation+ mGluR5 forward allosteric agent CDPPB group (group SD+ CDPPB), and sleep deprivation+ mGluR5 antagonist MPEP group (group SD+ MPEP). A 48-h sleep deprivation model was developed by sleep-deprived rod method. At the beginning of developing the model and 24 h after developing the model, CDPPB 10 mg/kg, MPEP 10 mg/kg and the equal volume of 1% Tween 80 were intraperitoneally injected in group SD+ CDPPB, group SD+ MPEP and group SD+ Vehicle, respectively.Morris water maze and novel object recognition tests were conducted to evaluate cognitive function after development of the model. The expression of Homer1a and mGluR5 in the hippocampus was detected by Western blot, the dendritic spine density in the hippocampal CA1 region was detected by Golgi staining, and the field excitatory postsynaptic potential (fEPSP) slope in the hippocampal CA1 region was detected by isolated electrophysiology. Results:Compared with Control group, the number of crossing the original platform, time of staying at the target quadrant, and novel object recognition index at 1 and 24 h after training were significantly decreased, the expression of Homer1a in the hippocampus was up-regulated, the expression of mGluR5 in the hippocampus was down-regulated, and the density of dendritic spine and fEPSP slope in the hippocampal CA1 region were decreased in group SD+ Vehicle ( P<0.05). Compared with group SD+ Vehicle, the number of crossing the original platform, time of staying at target quadrant, and novel object recognition index at 1 and 24 h after training were significantly increased, the expression of mGluR5 in hippocampus was up-regulated, and the density of dendritic spines and fEPSP slope in the hippocampal CA1 region were increased in group SD+ MPEP( P<0.05), and no statistically significant change was found in the parameters mentioned above in group SD+ CDPPB ( P>0.05). Conclusions:Sleep deprivation impairs the synaptic plasticity of hippocampal neurons by regulating Homer1a/mGluR5 signaling pathway, and thus mediating the process of cognitive dysfunction in aged rats.

The Interaction Between CAL and mGluR1 Alleviates Cytotoxicity Induced by mGluR1 Overactivation / 中国生物化学与分子生物学报

Glutamate excitotoxicity mediated by metabotropic glutamate receptor 1 (mGluR1) overexpression or overactivation plays an important role in the development of Parkinson's disease (PD). Although clinical trials support the therapeutic potential of certain mGluR negative allosteric modulators (NAMs), there are still some limitations of precise modulation of mGluR using NAMs. Thus, the identification of small molecules or endogenous genes that facilitate mGluR1 modulation might be potentially beneficial for PD treatment. We determined the role of interacting partner cystic fibrosis transmembrane conductance regulator-associated ligand (CAL) in overactivated mGluR1-mediated cell apoptosis and signaling pathway in vitro and in vivo. HEK293 cells were used as an experimental tool to directly examine the interaction between CAL and mGluR1. We found that agonist of mGluR1 significantly enhanced the interaction between CAL and mGluR1 (P< 0. 05). Furthermore, CAL suppressed overactivated mGluR1-induced cell apoptosis and the activation of mGluR1 downstream signaling pathways. CAL overexpression relieved rotenone-induced neuron death (P< 0. 001) by inhibiting the activation of mGluR1-mediated signaling pathways in rotenone-induced rat model of PD. This study may reveal a new mechanism of mGluR1 activity regulation, and hopefully provide a novel molecular mechanism for the nervous system related diseases.

Research progress of metabotropic glutamate receptor 5 in related central nervous system diseases / 中国药科大学学报

@#As a key component of glutamatergic system, metabotropic glutamate receptor 5 (mGluR5) has been extensively involved in the regulation of physiological processes such as synaptic transmission, synaptic plasticity and synaptic excitation/inhibition balance.Over the past few decades, mGluR5 has been found to be closely related to multiple neurological and psychiatric disorders, thus it is of considerable interest as a drug target in the treatment of such disorders.This review summarizes the structure and distribution of mGluR5, its normal physiological function, its pathological roles in related central nervous system (CNS) diseases, as well as the current status of its drug development, in order to provide reference for further investigation.

Receptores metabotrópicos de glutamato e sua relação com a Esclerose Lateral Amiotrófica (ELA) / Glutamate metabotropic receptors and its relationship with Amiotrophic Lateral Sclerosis (ALS)

A Esclerose Lateral Amiotrófica (ELA), uma doença neurodegenerativa fatal, que afeta neurônios motores superiores e inferiores, tem como fisiopatologia mais aceita a excitotoxicidade mediada por glutamato. O atual estudo tem como objetivo estabelecer a relação entre esse neurotransmissor e a ELA, a partir de uma revisão de literatura nas bases de dados Pubmed e Medline. O glutamato é o principal neurotransmissor do Sistema Nervoso Central (SNC) e a excitotoxicidade gerada pelo seu acúmulo nas fendas sinápticas é tida como um dos principais mecanismos envolvidos na fisiopatologia da ELA. Os indivíduos afetados pela ELA apresentam diminuição da expressão de determinados grupos de receptores metabotrópicos de glutamato (mGlu) nos neurônios e nas células da glia desses pacientes. Os mGlu possuem um papel de destaque na modulação da excitotoxicidade por glutamato e são subdivididos em três grupos. Os mGlus do grupo 1 amplificam as transmissões sinápticas excitatórias rápidas, e os dos grupos 2 e 3 atuam como neuroprotetores inibindo a liberação do glutamato na fenda sináptica. Os mGlus são, portanto, considerados alvos terapêuticos para a atuação de drogas que combatem a excitotoxicidade e induzem a produção de fatores neurotróficos, constituindo importante atuação no combate à ELA.

Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disease that affects upper and lower motor neurons, has as the most accepted pathophysiology the glutamate-mediated excitotoxicity. The present study aims to establish the relationship between this neurotransmitter and ALS, based on a literature review in the PubMed and Medline databases. Glutamate is the main neurotransmitter of the central nervous system (CNS) and the excitotoxicity generated by its accumulation in the synaptic clefts is considered one of the main mechanisms involved in the pathophysiology of ALS. People affected by ALS present a decrease in expression of certain metabotropic glutamate receptor (mGlu) groups in neurons and glial cells of these patients. mGlu has a prominent role in modulating glutamate excitotoxicity and are subdivided into three groups. Group 1 mGlu amplifies rapid excitatory synaptic transmissions, while groups 2 and 3 act as neuroprotective agents, since among other functions they inhibit glutamate release into the synaptic cleft. Finally, mGlu are considered therapeutic targets for the action of drugs that fight excitotoxicity and induce the production of neurotrophic factors, constituting an important action in the fight against ALS.

Activating mGluR8 Attenuates Visceral Hypersensitivity in Neonatal Maternally Separated Rats / 胃肠病学

Activating metabolite glutamate receptor 8 (mGluR8) has anti-hyperpathia effect in central nervous system, however, studies of effects in gastrointestinal tract are rare. Visceral hypersensitivity is one of the pathogenesis factors of irritable bowel syndrome (IBS). Aims: To investigate the effect and potential mechanism of activating mGluR8 on visceral hypersensitivity in neonatal maternally separated (NMS) rats. Methods: Twenty-four male newborn SD rats were randomly divided into normal control (NC) group, NMS group and mGluR8 agonist (S)-3, 4-DCPG group (3, 10 mg/kg). Newborn rats were subjected to 3 hours daily maternal separation on postnatal day 2-14 to establish the NMS model; in (S)-3, 4-DCPG group, (S)-3, 4-DCPG (3 or 10 mg/kg) were administered 1 hour prior to the visceral sensitivity test in NMS rats. Abdominal withdrawal reflex (AWR) score and abdominal electromyography (EMG) activity were used to measure visceral sensitivity. mGluR8 mRNA and protein expressions in colon mucosa were measured by RT-PCR and Western blotting, respectively; TNF-α, IL-1β and IL-6 mRNA expressions in colon mucosa were measured by RT-PCR. The protein expression of myeloperoxidase (MPO) was measured by immunohistochemistry. Results: AWR score and EMG activity in NMS group were significantly higher than those in NC group under different colorectal distension (CRD) pressure. AWR score and EMG activity were significantly decreased in (S)-3, 4-DCPG group. mGluR8 mRNA and protein expressions in NMS group were significantly higher than those in NC group (P<0.05). Compared with NMS group, TNF-α mRNA expression was significantly decreased in 3 mg/kg (S)-3, 4-DCPG group (P<0.05), and MPO protein expression was significantly decreased in 10 mg/kg (S)-3, 4-DCPG group (P<0.05). Conclusions: Activating mGluR8 attenuates visceral hypersensitivity in NMS rats, the mechanism may be related to decrease of pro-inflammatory cytokine TNF-α.

Regulatory effect of metabolic glutamate receptor 1 on maltolate aluminum-induced synaptic plasticity in rats / 中国职业医学

OBJECTIVE: To observe the effect of maltolate aluminum on synaptic plasticity in the hippocampus of rats and to explore the regulatory effect and mechanism of metabotropic glutamate receptor 1(mGluR1). METHODS: Specific pathogen free healthy adult male SD rats were randomly divided into control group, aluminum group, aluminum agonist group and aluminum antagonist group, 8 rats in each group. The rats in the control group received no treatment; the rats in aluminum group were injected with 5 μL 10 mmol/L maltolate aluminum solution into the lateral ventricle; the rats in aluminum agonists and aluminum antagonist group were injected with 3 μL 10 mmol/L maltolate aluminum solution plus 2 μL 0.1 μmol/L mGluR1 agonist or 2 μL 0.2 μmol/L mGluR1 antagonists into the lateral ventricle, respectively.Maltolate aluminum solution was injected every 2 days and continued for 10 days. After maltolate aluminum exposure, the amplitudes of long-term potentiation(LTP) in hippocampal CA1 region of rats were measured, and the relative expression levels of mRNA and protein of mGluR1, N-methyl-D-aspartate receptor(NMDAR1) and protein kinase C(PKC) in hippocampus tissue of rats were detected by real-time fluorescence quantitative polymerase chain reaction and Western blotting. RESULTS: The amplitude of LTP in hippocampal CA1 region in aluminum group and aluminum agonist group was lower than that in the control group and the aluminum antagonist group(P<0.05). Compared with the control group, the relative expression of mGluR1 mRNA and protein in the aluminum group increased, the relative expression of PKC and NMDAR1 mRNA and protein in the aluminum group decreased(P<0.05). Compared with the aluminum group, the relative expression of mGluR1 mRNA and protein in the aluminum agonist group increased, while the NMDAR1 mRNA decreased(P<0.05); the relative expression of mGluR1 mRNA and protein in the aluminum antagonist group decreased, while the NMDAR1 mRNA and protein increased(P<0.05). Compared with the aluminum agonist group, the relative expression of mGluR1 mRNA and protein decreased, while the NMDAR1 mRNA and protein increased in the aluminum antagonist group(P<0.05). The relative expression level of PKC mRNA and protein in aluminum agonist group and aluminum antagonist group was not statistically significant(P>0.05), and there was no statistical significance in these two groups compared with control group and aluminum group(P>0.05). CONCLUSION: Maltolate aluminum exposure can inhibit synaptic plasticity by inhibiting LTP in hippocampus of rats, and the mechanism may be related to the regulation of NMDAR1 expression by mGluR1.

Critical role of metabotropic glutamate receptor 4 in bone marrow-derived dendritic cells in the Th17 cell differentiation and the melanogenesis of B16 cells

Vitiligo is an acquired pigmentary disorder resulting from selective destruction of melanocytes. Emerging studies have suggested that T helper cell 17 (Th17) is potentially implicated in vitiligo development and progression. It was recently discovered that metabotropic glutamate receptor 4 (mGluR4) can modulate Th17-mediated adaptive immunity. However, the influence of mGluR4 on melanogenesis of melanocytes has yet to be elucidated. In the present study, we primarily cultured mouse bone marrow-derived dendritic cells (BMDC) and then knocked down and over-expressed mGluR4 using transfection. Transduced BMDC were co-cultured with CD4+ T cells and the expression of Th17-related cytokines were measured. The morphology and melanogenesis of B16 cells were observed after being treated with co-culture medium of CD4+ T cells and transduced BMDC. We found that mGluR4 knockdown did not affect the co-stimulatory CD80 and CD86 upregulation after lipopolysaccharide stimulation but did increase the expression of Th17-related cytokines, and further down-regulated the expression of microphthalmia-associated transcription factor (MITF) and the downstream genes, decreased melanin production, and destroyed the morphology of B16 cells. Conversely, over-expression of mGluR4 reduced the expression of CD80 and CD86, suppressed the production of Th17-related cytokines, increased the expression of MITF, and did not destroy the morphology of B16 cells. Our study confirmed that mGluR4 modulated the Th17 cell polarization and resulted in the alteration of melanogenesis and morphology of B16 cells. Collectively, these findings suggest mGluR4 might be a potent target involved in the immune pathogenesis of vitiligo.

Research progress in metabotropic glutamate receptor 5 and related nervous system diseases / 中国药理学与毒理学杂志

The metabotropic glutamate receptor 5 (mGluR5), one of the most important mGluRs, exerts a biological effect through the second messenger. mGluR5 is mainly distributed in the cerebral cortex, hippocampus, and striatum in the form of dimers. It participates in neuronal excitability network regulation, neurogenesis, and synaptic plasticity associated with learning and memory by activating signaling pathways such as protein kinase C-inositol 1, 4, 5-triphosphate-diacylglycerol-Ca2+ and phosphatidylinositol 3-kinase-mammalian target of Rapamycin. Recently, mGluR5 has been confirmed to play an important role in diseases of the nervous system. Studies have shown that over-activation or inhibition of mGluR5 is closely related to the pathological processes of a variety of neurological diseases. A variety of drugs that selectively activate or inhibit mGluR5 activity have been used in the treatment of neurological diseases.

Role of group mGluR in low dose ketamine protecting learning and memory function after electroconvulsive shock in depression rats / 上海交通大学学报（医学版）

Objective • To investigate the role of group I metabotropic glutamate receptor (mGluR) in the regulation of N-methyl-D-aspartic acid receptor (NMDAR)-mediated synaptic plasticity in low dose ketamine protecting learning and memory function after modified electroconvulsive shock (MECS). Methods • The 2-3-month-old Sprague Dawley (SD) rats were used to establish depression models with chronic unpredictable mild stress. Ten healthy rats were used as the control group (group C), and another 30 depressed rats were randomly divided into group D, group M, and group KM. Group C was not treated, group D was treated with pseudo-MECS after intraperitoneal injection of normal saline, group M was given intraperitoneal injection of propofol, and group KM was given intraperitoneal injection of propofol combined with low-dose ketamine (10 mg/kg). Both group M and group KM underwent MECS. The sucrose preference test was used to evaluate the depression status. The Morris water maze was used to detect the spatial learning and memory function. The expression of NMDAR1, mGluR1 and mGluR5 proteins in the hippocampus was detected by Western blotting. Another 36 depressed rats were randomly divided into 6 groups: group DE, group m1E, group m5E, group DE', group m1E', and group m5E'. Group DE and group DE' were perfused with artificial cerebrospinal fluid alone. Group m1E and group m1E' were perfused with artificial cerebrospinal fluid containing mGluR1 blocker. Group m5E and group m5E' were perfused with artificial cerebrospinal fluid containing mGluR5 blocker. Long-term potentiations (LTP) were detected in group DE, group m1E, and group m5E. NMDAR-mediated field potentials (fEPSPNMDAR) were detected in group DE', group m1E', and group m5E'. Results • After treatment, the sucrose preference percentages of group M and group KM increased compared with group D (P<0.05), the escape latencies (EL) of group M and group KM were prolonged (P<0.05), and the space exploration times (SET) were shortened (P<0.05). Compared with group M, the EL of group KM was shortened (P<0.05), and the SET was prolonged (P<0.05). Compared with group D, the expression levels of NMDAR1, mGluR1 and mGluR5 in group M and group KM decreased (P<0.05). Compared with group M, the expression levels of NMDAR1, mGluR1 and mGluR5 in group KM increased (P<0.05). Compared with group DE, the LTP decreased in group m1E and group m5E (P<0.05). Compared with group DE', the fEPSPNMDAR of group m1E' and group m5E' decreased (P<0.05). Conclusion • Ketamine up-regulates NMDAR1 and group mGluR expression to enhance the activation of NMDAR in the hippocampus which may be responsible for the protective effects on spatial learning and memory function in depression rats undergoing MECS.

Regulatory Effects of Ionotropic and GroupⅠ Metabotropic Glutamate Receptors on Temperature Hypersensitivity in Rats / 中国医科大学学报

Objective To study the effects of ionic and group Ⅰ metabotropic glutamate receptors on rats' thermal hypersensitivity by intraplantar administration of drugs. Methods After intraplantar administration of glutamate receptor agonists,L-glutamic acid (Glu), N-methyl-D-aspartic-acid (NMDA),and (RS)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid hydrobromide (AMPA);a Group Ⅰ mGluR agonist, (S) 3,5-dihydroxyphenylglycine [(S)-DHPG];a noncompetitive NMDA receptor antagonist, (+)-MK801 maleate (MK-801);a competitive AMPA/kainate receptor antagonist,6-cyano-7-nitroquinoxaline-2,3-dione (CNQX);and a selective GroupⅠ mGluR antagonist,7-hydroxyiminocyclo propan[b]chromen-1a- carboxylic acid ethyl ester (cpccoEt) into the left hind paws of rats whose L5-6 nerves were sham-operated or ligated,we examined the response of the rats to thermal stimuli provided by radiant heat. Results In sham-operated rats,glutamate,NMDA,AMPA,and (S)-DHPG reduced paw withdrawal latency (PWL) but did not have any effect on SNL rats. However,in SNL rats,MK-801,CNQX,and cpccoEt increased PWL but exerted no effect on sham-operated rats. Conclusion These results suggest that changes in sensitivity of peripheral ionic and group Ⅰ metabotropic glutamate receptors can lead to changes in peripheral nerve plasticity;the generation and maintenance of neuropathic pain caused by nerve injury is based on this plasticity.

Protective effect of metabotropic glutamate receptor 1 negative allosteric modulator JNJ16259685 on neuron after subarachnoid hemorrhage in rats / 中国脑血管病杂志

Objective To investigate the protective effect and its mechanism of metabotropic glutamate receptor 1 ( mGluR1) negative allosteric modulator JNJ16259685 on neuron after subarachnoid hemorrhage (SAH) in rats. Methods Ninety SPF-grade SD male rats were selected. They were randomly divided into 3 groups:sham operation group (n=18),SAH+placebo group (n=36),and SAH+JNJ16259685(JNJ) group (n=36). A SAH model was induced by intravascular puncture. SAH +placebo group received intraperitoneal injection of aseptic water containing 5% dimethyl sulfoxide (DMSO) at 2,24 and 48 h after operation. The SAH+JNJ group was intraperitoneally injected with 1 mg/kg JNJ16259685 ( dissolved in sterile water in 5% DMSO). Garcia scoring criteria were used to assess neurological deficits at 72 h after SAH. Dry and wet weight method was used to detect brain edema. Evans Blue method was used to assess blood-brain barrier permeability. A calcium assay kit was used to detect the mitochondrial calcium ion concentration. Immunofluorescence staining was used to observe neuronal apoptosis. GraphPad 7. 0 software was used to conduct one-way analysis of variance in all indicators among the 3 groups. Results Compared with the sham operation group,the Garcia score (11. 0 ± 0. 4) decreased in the SAH+placebo group. The water content in left and right hemispheres was 80. 5 ± 0. 1% and 80. 3 ± 0. 2% respectively,the Evans blue dye extravasation (2. 8 ± 0. 2),basal cortical mitochondrial calcium ion concentration (2. 5 ± 0. 3),and neuronal apoptosis in basal cortex and hippocampus CA1 region (the number of active caspase-3/NeuN positive cells was 300 ±30/mm2and 20 ± 2/mm respectively) increased (all P<0. 05);and the Garcia score (13. 0 ± 0. 5) was significantly higher in the SAH+JNJ group than in the SAH+placebo group. Water content in left and right hemispheres was 79. 8 ± 0. 2% and 79. 3 ± 0. 1% respectively,Evans blue dye extravasation (1. 8 ±0. 2),basal cortex mitochondrial calcium ion concentration (1. 7 ± 0. 1),basal cortex and the number of neuronal apoptosis in hippocampal CA1 region (the number of active caspase-3/NeuN positive cells were 180 ± 10/mm2,12 ±2/mm) reduced compared with the SAH+placebo group (all P<0. 05). Conclusion After SAH,JNJ16259685 relieves cerebral edema and reduces blood-brain barrier permeability,inhibits the increase of cortical mitochondrial calcium ion concentration,and reduces neuronal apoptosis,thereby exerting neuroprotective effects.

Effect of Serum on Cultured Astrocytes Morphology and Expression of Aquaporin-4 in Rats / 中国康复理论与实践

Objective To explore the effect of blood-brain barrier disruption on expression of AQP-4,through comparing the cell morphology and the expression of aquaporin-4(AQP-4)of cultured astrocytes in medium with and without fetal bovine serum(FBS). Methods Cerebral cortical astrocytes from female Wistar rats were cultured in serum free medium,DMEM supplement-ed with 10% FBS,and serum free medium supplemented with 10% FBS.Phase contrast microscope was used to detect the cell morphology and cell size. Immunofluorescence staining and reverse real-time quantitative poly-merase chain reaction(RT-qPCR)were used to examine the expression of glial fibrillary acidic protein(GFAP), AQP-4 and metabotropic glutamate receptor 5(mGluR5). Results Astrocytes in serum free medium showed extensive process bearing morphology,small body and nucleus,and high refractivity.In contrast,in two kinds of 10% FBS-containing medium,astrocytes were flat with large body and nucleus,weak refractivity,as well as short process.Analysis of immunofluorescence staining and RT-qPCR revealed a down-regulation of GFAP and AQP-4 protein and mRNA expression in two kinds of 10% FBS-con-taining medium, compared with that in serum free medium (P<0.001), however, there was no difference in mGluR5 protein and mRNA expression(P>0.05). Conclusion FBS changed astrocyte morphology and down-regulated the expression of GFAP and AQP-4.

Relationship between metabotropic glutamate receptor 5 and N-methyl-D-aspartate receptor and their roles in diseases / 上海交通大学学报（医学版）

Metabotropic glutamate receptor 5 (mGluR5) and N-methyl-D-aspartate receptor (NMDAR) belongs to metabotropic and ionotropic glutamate receptor family, respectively. In recent years, a lot of attention has been paid to these two types of glutamate receptors in the field of neuroscience and psychiatry. This article mainly summarized the research progress of the relationship between these two kinds of receptors and the influence of their relationship on different diseases.

Metabotropic glutamate receptor 5 may be involved in macrophage plasticity

Abstract Background Macrophages are a functionally heterogeneous cell population and depending on microenvironments they polarize in two main groups: M1 and M2. Glutamic acid and glutamate receptors may participate in the regulation of macrophage plasticity. To investigate the role of glutamatergic systems in macrophages physiology, we performed the transfection of mGluR5 cDNAs into RAW-264.7 cells. Results Comparative analysis of modified (RAW-mGluR5 macrophages) and non-modified macrophages (RAW-macrophages) has shown that the RAW-mGluR5 macrophages absorbed more glutamate than control cells and the amount of intracellular glutamate correlated with the expression of excitatory amino acid transporters -2 (EAAT-2). Besides, our results have shown that RAW-mGluR5 macrophages expressed a higher level of peroxisome proliferator-activated receptor γ (PPAR-γ) and secreted more IL-10, high mobility group box 1 proteins (HMGB1) and Galectin-3 than control RAW-macrophages. Conclusions We propose that elevation of intracellular glutamate and expression of mGluR5 may initiate the metabolic rearrangement in macrophages that could contribute to the formation of an immunosuppressive phenotype.

Metabotropic glutamate receptor 5 and related clinical diseases / 基础医学与临床

mGlu5 (Metabotropic glutamate receptor 5) does not only exist in nervous system , but also in many pe-ripheric organs and tissues .The vital role that mGlu5 plays in both nervous and non-nervous system diseases , which will be important for further studying the pathogenesis of diseases .Moreover, it can provide us with new ide-as and methods for precaution and cure of illness with mGluRs .

Role of Principal Ionotropic and Metabotropic Receptors in Visceral Pain

Visceral pain is the most common form of pain caused by varied diseases and a major reason for patients to seek medical consultation. It also leads to a significant economic burden due to workdays lost and reduced productivity. Further, long-term use of non-specific medications is also associated with side effects affecting the quality of life. Despite years of extensive research and the availability of several therapeutic options, management of patients with chronic visceral pain is often inadequate, resulting in frustration for both patients and physicians. This is, most likely, because the mechanisms associated with chronic visceral pain are different from those of acute pain. Accumulating evidence from years of research implicates several receptors and ion channels in the induction and maintenance of central and peripheral sensitization during chronic pain states. Understanding the specific role of these receptors will facilitate to capitalize on their unique properties to augment the therapeutic efficacy while at the same time minimizing unwanted side effects. The aim of this review is to provide a concise review of the recent literature that reports on the role of principal ionotropic receptors and metabotropic receptors in the modulation visceral pain. We also include an overview of the possibility of these receptors as potential new targets for the treatment of chronic visceral pain conditions.

Expression of Glu、mGluR 5 and EAAT 1 in bone tissues of ovariectomized osteoporotic rats and the effects of Total Flavonoids of Rhizoma Drynariae on it / 中国生化药物杂志

Objective To observe the expression of Glu、mGluR 5 and EAAT 1 in bone tissues of ovariectomized osteoporotic rats and the effects of Total Flavonoids of Rhizoma Drynariae (TFRD) on it. Methods 45 SPF 3-month-old Sprague-Dawley (SD) female rats were randomly divided into sham operation (Sham, n=15) group and ovariectomized (OVX, n=30) group. The osteoporotic(OP) model was established by bilateral ovariectomy, 14 weeks later, we measured bone mineral density(BMD) by dual-energy X-ray and determined that OP model was successfully replicated, OVX group rats were then divided into OVX group (n=15) and OVX+TFRD group (n=15). The OVX+TFRD group was given TFRD for 12 weeks. Glutamate (Glu), metabotropic glutamate receptor 5 (mGluR 5), and Glutamate/Aspartate Transporter (GLAST/EAAT 1)’s expression of femur was examined in order to clarify the characteristics of bone glutamate signaling pathway and the effects of TFRD on it. Results Glu and ionotropic receptors mGluR 5 mainly distributed in bone marrow cells and osteoblasts closed to the bone marrow cavity walls. There were no significant differences in Glu expression among Sham group, OVX group and OVX+TFRD group. The mGluR 5 expression of OVX+TFRD group was significantly higher than that of Sham group and OVX group(P=0.009), while no significant difference was found between the latter two groups. In addition to large distribution in bone marrow cells, small amount of transporter EAAT 1 was noted to express in bone cells of the bone lacunae. There were no significant differences in EAAT 1 expression among the three groups. Conclusion In bone glutamate signaling pathway, this study demonstrated that TFRD could significantly improve the ionotropic receptor mGluR 5’s expression, but had no inlfuence for Glu and EAAT 1.

Regulation of metabotropic glutamate subtype 7 and 8 receptors in nucleus tractus solitarius in cardiac nociception in rats / 吉林大学学报(医学版)

Objective To explore the role of metabotropic glutamate receptors (mGluRs)group Ⅲ and its subtypes mGluR7 and mGluR8 in nucleus tractus solitarius(NTS)in cardiac-somatic motor reflex (CMR),and to clarify the modulation role of mGluR Ⅲ and its subtypes in NTS in cardiac nociceptoion.Methods 40 SD rats were randomly divided into L-AP4 group,microinjection of mGluRs Ⅲ agonist L-AP4 0.1,1.0,10.0 or 20.0 nmol in NTS;AMN082 group,microinjection of mGluR7 agonist AMN082 1,2 or 4 nmol;DCPG group,microinjection of mGluR8 agonist DCPG 4, 6 or 8 nmol;MSOP group, microinjection of mGluR Ⅲ antagonist MSOP 20 or 100 nmol,20 nmol MSOP+410 nmol L-AP,20 nmol MSOP+2 nmol AMN082,20 nmol MSOP+6 nmol DCPG. The changes of CMR of the rats in various groups were observed.Results Compared with control,the CMR in L-AP4 and AMN082 groups was decreased (P0.05);the CMR in MSOP group after injection of 100 nmol MSOP was increased (P0.05).Conclusion The group Ⅲ mGluRs in the NTS play an inhibitory role in cardiac nociception, and mGluR7 has anti-nociceptive effects while mGluR8 has pro-nociceptive effects.

Expression of Metabotropic Glutamate Receptors in the Medial Vestibular Nucleus Following Acute Hypotension in Rats / 대한평형의학회지

BACKGROUND AND OBJECTIVES: Acute hypotension induces expression of c-Fos protein and phosphorylated extracellular signal-regulated kinase (pERK), and glutamate release in the vestibular nuclei. Expression of c-Fos protein and pERK is mediated by the excitatory neurotransmitter, glutamate. In this study, the signaling pathway of glutamate in the vestibular nuclei following acute hypotension was investigated. MATERIALS AND METHODS: Expression of metabotropic glutamate receptors (mGluRs) was measured by Western blotting in the medial vestibular nucleus following acute hypotension in rats. RESULTS: Expression of pGluR1 Ser831, a subtype of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, peaked at 30 minutes after acute hypotension insult, and expression of pNR2B, a subtype of N-methyl-D-aspartate (NMDA) receptors, peaked at 2 hours after acute hypotension insult. Acute hypotension induced expression of Homer1a and group I mGluR in the medial vestibular nucleus. Expression of mGluR1 and mGluR5 peaked at 6 hours following acute hypotension insults. CONCLUSION: These results suggest that afferent signals from the peripheral vestibular receptors, resulting from acute hypotension insult, are transmitted through group I mGluRs as well as AMPA and NMDA receptors in the vestibular system.