1.Spinal Metabotropic Glutamate Receptors (mGluRs) are Involved in the Melittin-induced Nociception in Rats.
The Korean Journal of Physiology and Pharmacology 2008;12(5):237-243
Intraplantar injection of melittin has been known to induce sustained decrease of mechanical threshold and increase of spontaneous flinchings. The present study was undertaken to investigate how the melittin-induced nociceptive responses were modulated by changes of metabotropic glutamate receptor (mGluR) activity. Changes in paw withdrawal threshold (PWT), number of flinchings and paw thickness were measured at a given time point after injection of melittin (10microgram/paw) into the mid-plantar area of rat hindpaw. To observe the effects of mGluRs on the melittin-induced nociceptions, group I mGluR (AIDA, 100microgram and 200microgram), mGluR1 (LY367385, 50microgram and 100microgram) and mGluR5 (MPEP, 200microgram and 300microgram) antagonists, group II (APDC, 100microgram and 200microgram) and III (L-SOP, 100microgram and 200microgram) agonists were intrathecally administered 20 min before melittin injection. Intraplantar injection of melittin induced a sustained decrease of mechanical threshold, spontaneous flinchings and edema. The effects of melittin to reduce mechanical threshold and to induce spontaneous flinchings were significantly suppressed following intrathecal pre-administration of group I mGluR, mGluR1 and mGluR5 antagonists, group II and III mGluR agonists. Group I mGluR antagonists and group II and III mGluR agonists had no significant effect on melittin-induced edema. These experimental findings indicate that multiple spinal mGluRs are involved in the modulation of melittin-induced nociceptive responses.
Animals
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Edema
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Melitten
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Nociception
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Rats
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Receptors, Metabotropic Glutamate
2.Modulation of Amygdala Synaptic Transmission by Metabotropic Glutamate Receptors.
Jung Hyun KIM ; Eun Jin PARK ; Duk Jin CHANG ; Sukwoo CHOI
The Korean Journal of Physiology and Pharmacology 2003;7(6):303-306
Metabotropic glutamate receptors (mGluRs), classified into three groups (group I, II, III), play a critical role in modulation of synaptic transmission at central and peripheral synapses. In the present study, extracellular field potential recording techniques were used to investigate effects of mGluR agonists on excitatory synaptic transmission at thalamic input synapses onto the lateral amygdala. The non-selective mGluR agonist t-ACPD (100 microM) produced reversible, short-term depression, but the group III mGluR agonist L-AP4 (50 microM) did not have any significant effects on amygdala synaptic transmission, suggesting that group I and/or II mGluRs are involved in the modulation by t-ACPD. The group I mGluR agonist DHPG (100 microM) produced reversible inhibition as did t-ACPD. Unexpectedly, the group II mGluR agonist LCCG-1 (10 microM) induced long-term as well as short-term depression. Thus, our data suggest that activation of group I or II mGluRs produces short-term, reversible depression of excitatory synaptic transmission at thalamic input synapses onto the lateral amygdala. Considering the long-term effect upon activation of group II mGluRs, lack of long-term effects upon activation of group I and II mGluRs may indicate a possible cross-talk among different groups of mGluRs.
Amygdala*
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Depression
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Receptors, Metabotropic Glutamate*
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Synapses
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Synaptic Transmission*
5.Effects of Apigenin on Glutamate-induced Ca2+i Increases in Cultured Rat Hippocampal Neurons.
Ji Hwa HAN ; Ki Jung KIM ; Hyun Jong JANG ; Ju Ho JANG ; Myung Jun KIM ; Ki Wug SUNG ; Duck Joo RHIE ; Yang Hyeok JO ; Sang June HAHN ; Mun Yong LEE ; Shin Hee YOON
The Korean Journal of Physiology and Pharmacology 2008;12(2):43-49
Flavonoids have been shown to affect calcium signaling in neurons. However, there are no reports on the effect of apigenin on glutamate-induced calcium signaling in neurons. We investigated whether apigenin affects glutamate-induced increase of free intracellular Ca2+concentration ([Ca2+]i) in cultured rat hippocampal neurons, using fura-2-based digital calcium imaging and microfluorimetry. The hippocampal neurons were used between 10 and 13 days in culture from embryonic day 18 rats. Pretreatment of the cells with apigenin (1micrometerto 100micrometer for 5 min inhibited glutamate (100 micrometer 1 min) induced [Ca2+]i increase, concentration-dependently. Pretreatment with apigenin (30micrometer for 5 min significantly decreased the [Ca2+]i responses induced by two ionotropic glutamate receptor agonists, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA, 10 micrometer 1 min) and N-methyl-D-aspartate (NMDA, 100 micrometer 1 min), and significantly inhibited the AMPA-induced peak currents. Treatment with apigenin also significantly inhibited the [Ca2+]i response induced by 50 mM KCl solution, decreased the [Ca2+]i responses induced by the metabotropic glutamate receptor agonist, (S)-3,5-dihydroxyphenylglycine (DHPG, 100micrometer 90 s), and inhibited the caffeine (10 mM, 2 min)-induced [Ca2+]i responses. Furthermore, treatment with apigenin (30micrometer significantly inhibited the amplitude and frequency of 0.1 mM [Mg2+o-induced [Ca2+]i spikes. These data together suggest that apigenin inhibits glutamate-induced calcium signaling in cultured rat hippocampal neurons.
Animals
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Apigenin
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Caffeine
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Calcium
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Calcium Signaling
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Glutamic Acid
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N-Methylaspartate
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Neurons
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Rats
;
Receptors, Glutamate
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Receptors, Metabotropic Glutamate
6.Developmental expression and cellular distribution of metabotropic glutamate receptor 5 in the frontal cortex of human fetus.
Wuling XIE ; Pengbo YANG ; Junfeng ZHANG ; Xinli XIAO ; Hui JIN ; Qindong SHI ; Xi XU ; Yong LIU
Journal of Southern Medical University 2012;32(4):443-448
OBJECTIVETo investigate the expression of metabotropic glutamate receptor 5 (mGluR5) and its cellular distribution in the frontal cortex, ventricular zone (VZ) and subventricular zone (SVZ) in human fetuses.
METHODSAccording to the gestational age, the collected fetuses were divided into 4 groups, namely 9-11 weeks, 14-16 weeks, 22-24 weeks and 32-36 weeks. Brain tissue blocks including the frontal lobe or VZ/SVZ were prepared into slices, and the expression pattern and cellular distribution of mGluR5 in the frontal cortex and VZ/SVZ were observed by immunohistochemistry or immunofluorescence.
RESULTSmGluR5 immunoreactivity was present in the cell membrane in the frontal cortex, VZ and SVZ from the 9th to 36th weeks and the immunoreactivity in the marginal zone (MZ) and cortical plate (CP) was markedly stronger than that in VZ and SVZ. The cells expressing mGluR5 included neural stem/progenitor cells in the VZ and SVZ, immature neurons in the VZ and MZ, and numerous mature neurons in the CP.
CONCLUSIONmGluR5 is expressed by a variety of cells such as neural stem cells in the frontal cortex, VZ and SVZ in human fetus, suggesting a role of mGluR5 in the development of human cerebral cortex.
Cerebral Cortex ; cytology ; Cerebral Ventricles ; cytology ; metabolism ; Fetus ; cytology ; metabolism ; Frontal Lobe ; cytology ; metabolism ; Humans ; Neural Stem Cells ; cytology ; metabolism ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate ; metabolism
7.Expression change of mGluR5 in rat MVN after unilateral labyrinthectomy.
Yamin ZHANG ; Weijia KONG ; Yujuan HU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2009;23(10):456-459
OBJECTIVE:
To observe the expression of mGluR5 in the medial vestibular nucleus (MVN) following unilateral labyrinthectomy (UL).
METHOD:
Thirty Wistar rats were randomly divided into two groups. Twenty four animals received unilateral labyrinthectomy while the others maintained labyrinthine well. After setting left labyrinthine, the change of mGluR5 was induced by immunohistochemistry, in situ hybridization.
RESULT:
mGluR5 was increased in lesioned side MVN after unilateral labyrinthectomy. The 12 h post-UL was highest. Then it was decrease in 36 h post-UL, while 7 d post-UL was same as control group. The change of contralateral was same as that in ipsilateral.
CONCLUSION
UL can induce increase of mGluR5 in the MVN. The reduced resting discharge in the primary vestibular afferents or in the central vestibular neurons may be responsible for the change of mGluR5. However the significance of the change of mGluR1 in the vestibular compensation is still unknown.
Animals
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Male
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Postoperative Period
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Rats
;
Rats, Wistar
;
Receptor, Metabotropic Glutamate 5
;
Receptors, Metabotropic Glutamate
;
metabolism
;
Vestibular Nuclei
;
metabolism
;
Vestibule, Labyrinth
;
metabolism
;
surgery
8.Expression of group I mGluRs in rat flocculus after unilateral labyrinthectomy.
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2009;23(13):604-606
OBJECTIVE:
Studies revealed that cerebellar flocculus-paraflocculus complex plays an important in vestibular compensation. To observe the expression change of Group I mGluRs in flocculus following left unilateral labyrinthectomy (UL).
METHOD:
After setting left labyrinthectomy, the change of Group I mGluRs was detected by RT-PCR.
RESULT:
Group I mGluR5 was induced increase in both side flocculus after unilateral labyrinthectomy. By contrast, mGluR1 was induced decrease. However, that of the lesioned side was stronger than that of the unlesioned side.
CONCLUSION
UL can induce change of Group I mGluRs in the flocculus. The fall in the resting discharge of the primary vestibular afferents and/or in the deafferented central vestibular neurons may cause the change of mGluRs. But the significance of the change of mGluRs in the vestibular compensation is still unknown.
Animals
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Cerebellar Nuclei
;
metabolism
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Male
;
Rats
;
Rats, Wistar
;
Receptor, Metabotropic Glutamate 5
;
Receptors, Metabotropic Glutamate
;
metabolism
;
Vestibular Nuclei
;
metabolism
;
Vestibule, Labyrinth
;
metabolism
9.The Role of Metabotropic Glutamate Receptors in Psychomotor Stimulant Addiction.
Jeong Hoon KIM ; Hye Kyoung PARK
Korean Journal of Psychopharmacology 2006;17(2):143-148
For many years, determining the role of dopamine has been the major focus of the drug abuse research. New evidence, however, suggests that glutamate may play more important roles in the process of development of addictive behaviors. Metabotropic glutamate receptors are abundant in the brain and known to consist of three different groups of subtypes. Experimental data apparently show that they, especially group I and II, have important roles in the process of behaviors indicative of addiction such as locomotor activity, behavioral sensitization, conditioned place preference by psychomotor stimulants, and self-administration of these drugs. Although it has not been yet discovered how they differentially regulate neuronal processes to produce addictive behaviors, they have been suggested as a new possible therapeutic target for the treatment of drug addiction.
Behavior, Addictive
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Brain
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Dopamine
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Glutamic Acid
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Motor Activity
;
Neurons
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Receptors, Metabotropic Glutamate*
;
Substance-Related Disorders
10.TRPC-Mediated Current Is Not Involved in Endocannabinoid-Induced Short-Term Depression in Cerebellum.
Wonseok CHANG ; Joo Min PARK ; Jun KIM ; Sang Jeong KIM
The Korean Journal of Physiology and Pharmacology 2012;16(2):139-144
It has been reported that activation of metabotropic glutamate receptor 1 (mGluR1) can mediate endocannabinoid-induced short-term depression of synaptic transmission in cerebellar parallel fiber (PF)-Purkinje cell (PC) synapse. mGluR1 has signaling pathways involved in intracellular calcium increase which may contribute to endocannabinoid release. Two major mGluR1-evoked calcium signaling pathways are known: (1) slow-kinetic inward current carried by transient receptor potential canonical (TRPC) channel which is permeable to Ca2+; (2) IP3-induced calcium release from intracellular calcium store. However, it is unclear how much each calcium source contributes to endocannabinoid signaling. Here, we investigated whether calcium influx through mGluR1-evoked TRPC channel contributes to endocannabinoid signaling in cerebellar Purkinje cells. At first, we applied SKF96365 to inhibit TRPC, which blocked endocannabinoid-induced short-term depression completely. However, an alternative TRP channel inhibitor, BTP2 did not affect endocannabinoid-induced short-term depression although it blocked mGluR1-evoked TRPC currents. Endocannabinoid signaling occurred normally even though the TRPC current was mostly blocked by BTP2. Our data imply that TRPC current does not play an important role in endocannabinoid signaling. We also suggest precaution in applying SKF96365 to inhibit TRP channels and propose BTP2 as an alternative TRPC inhibitor.
Calcium
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Calcium Signaling
;
Cerebellum
;
Depression
;
Endocannabinoids
;
Imidazoles
;
Purkinje Cells
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Receptors, Metabotropic Glutamate
;
Synapses
;
Synaptic Transmission