Stimulation of group II metabotropic glutamate receptors or inhibition of group I ones exerts anxiolytic-like effects in rats

Amino Acids ◽  
2000 ◽  
Vol 19 (1) ◽  
pp. 81-86 ◽  
Author(s):  
A. Pilc ◽  
E. Chojnacka-Wójcik ◽  
E. Tatarczyńska ◽  
J. Borycz ◽  
B. Kroczka
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Group Ii ◽  
Stimulation Of

Groups II and III Metabotropic Glutamate Receptors Differentially Modulate Brief and Prolonged Nociception in Primate STT Cells

2000 ◽  
Vol 84 (6) ◽  
pp. 2998-3009 ◽  
Author(s):  
Volker Neugebauer ◽  
Ping-Sun Chen ◽  
William D. Willis
Keyword(s):  
Glutamate Receptors ◽  
Dorsal Horn ◽  
Central Sensitization ◽  
Metabotropic Glutamate Receptors ◽  
Background Activity ◽  
Mechanical Stimuli ◽  
Group Iii ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Group Ii

The heterogeneous family of G-protein-coupled metabotropic glutamate receptors (mGluRs) provides excitatory and inhibitory controls of synaptic transmission and neuronal excitability in the nervous system. Eight mGluR subtypes have been cloned and are classified in three subgroups. Group I mGluRs can stimulate phosphoinositide hydrolysis and activate protein kinase C whereas group II (mGluR2 and 3) and group III (mGluR4, 6, 7, and 8) mGluRs share the ability to inhibit cAMP formation. The present study examined the roles of groups II and III mGluRs in the processing of brief nociceptive information and capsaicin-induced central sensitization of primate spinothalamic tract (STT) cells in vivo. In 11 anesthetized male monkeys ( Macaca fascicularis), extracellular recordings were made from 21 STT cells in the lumbar dorsal horn. Responses to brief (15 s) cutaneous stimuli of innocuous (brush), marginally and distinctly noxious (press and pinch, respectively) intensity were recorded before, during, and after the infusion of group II and group III mGluR agonists into the dorsal horn by microdialysis. Different concentrations were applied for at least 20 min each (at 5 μl/min) to obtain cumulative concentration-response relationships. Values in this paper refer to the drug concentrations in the microdialysis fibers; actual concentrations in the tissue are about three orders of magnitude lower. The agonists were also applied at 10–25 min after intradermal capsaicin injection. The group II agonists (2S,1′S,2′S)-2-(carboxycyclopropyl)glycine (LCCG1, 1 μM-10 mM, n = 6) and (−)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268; 1 μM-10 mM, n = 6) had no significant effects on the responses to brief cutaneous mechanical stimuli (brush, press, pinch) or on ongoing background activity. In contrast, the group III agonist L(+)-2-amino-4-phosphonobutyric acid (LAP4, 0.1 μM-10 mM, n = 6) inhibited the responses to cutaneous mechanical stimuli in a concentration-dependent manner, having a stronger effect on brush responses than on responses to press and pinch. LAP4 did not change background discharges significantly. Intradermal injections of capsaicin increased ongoing background activity and sensitized the STT cells to cutaneous mechanical stimuli (ongoing activity > brush > press > pinch). When given as posttreatment, the group II agonists LCCG1 (100 μM, n = 5) and LY379268 (100 μM, n = 6) and the group III agonist LAP4 (100 μM, n = 6) reversed the capsaicin-induced sensitization. After washout of the agonists, the central sensitization resumed. Our data suggest that, while activation of both group II and group III mGluRs can reverse capsaicin-induced central sensitization, it is the actions of group II mGluRs in particular that undergo significant functional changes during central sensitization because they modulate responses of sensitized STT cells but have no effect under control conditions.

Antagonists reversibly reverse chemical LTD induced by group I, group II and group III metabotropic glutamate receptors

2013 ◽  
Vol 74 ◽  
pp. 135-146 ◽  
Author(s):  
David Lodge ◽  
Patrick Tidball ◽  
Marion S. Mercier ◽  
Sarah J. Lucas ◽  
Lydia Hanna ◽  
...  
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Group Iii ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Group Ii

scholarly journals Metabotropic glutamate receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Francine Acher ◽  
Giuseppe Battaglia ◽  
Hans Bräuner-Osborne ◽  
P. Jeffrey Conn ◽  
Robert Duvoisin ◽  
...  
Keyword(s):  
Glutamate Receptors ◽  
G Protein ◽  
Metabotropic Glutamate Receptors ◽  
Transmembrane Domain ◽  
Acid Group ◽  
Allosteric Modulators ◽  
Group Iii ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Group Ii

Metabotropic glutamate (mGlu) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Metabotropic Glutamate Receptors [334]) are a family of G protein-coupled receptors activated by the neurotransmitter glutamate. The mGlu family is composed of eight members (named mGlu1 to mGlu8) which are divided in three groups based on similarities of agonist pharmacology, primary sequence and G protein coupling to effector: Group-I (mGlu1 and mGlu5), Group-II (mGlu2 and mGlu3) and Group-III (mGlu4, mGlu6, mGlu7 and mGlu8) (see Further reading).Structurally, mGlu are composed of three juxtaposed domains: a core G protein-activating seven-transmembrane domain (TM), common to all GPCRs, is linked via a rigid cysteine-rich domain (CRD) to the Venus Flytrap domain (VFTD), a large bi-lobed extracellular domain where glutamate binds. The structures of the VFTD of mGlu1, mGlu2, mGlu3, mGlu5 and mGlu7 have been solved [190, 262, 255, 386]. The structure of the 7 transmembrane (TM) domains of both mGlu1 and mGlu5 have been solved, and confirm a general helical organization similar to that of other GPCRs, although the helices appear more compacted [85, 415, 59]. mGlu form constitutive dimers crosslinked by a disulfide bridge. Recent studies revealed the possible formation of heterodimers between either group-I receptors, or within and between group-II and -III receptors [86]. Although well characterized in transfected cells, co-localization and specific pharmacological properties also suggest the existence of such heterodimers in the brain [422, 257]. The endogenous ligands of mGlu are L-glutamic acid, L-serine-O-phosphate, N-acetylaspartylglutamate (NAAG) and L-cysteine sulphinic acid. Group-I mGlu receptors may be activated by 3,5-DHPG and (S)-3HPG [29] and antagonized by (S)-hexylhomoibotenic acid [223]. Group-II mGlu receptors may be activated by LY389795 [256], LY379268 [256], eglumegad [337, 416], DCG-IV and (2R,3R)-APDC [338], and antagonised by eGlu [161] and LY307452 [408, 100]. Group-III mGlu receptors may be activated by L-AP4 and (R,S)-4-PPG [125]. An example of an antagonist selective for mGlu receptors is LY341495, which blocks mGlu2 and mGlu3 at low nanomolar concentrations, mGlu8 at high nanomolar concentrations, and mGlu4, mGlu5, and mGlu7 in the micromolar range [176]. In addition to orthosteric ligands that directly interact with the glutamate recognition site, allosteric modulators that bind within the TM domain have been described. Negative allosteric modulators are listed separately. The positive allosteric modulators most often act as ‘potentiators’ of an orthosteric agonist response, without significantly activating the receptor in the absence of agonist.

Modulation of mEPSCs in Olfactory Bulb Mitral Cells by Metabotropic Glutamate Receptors

1997 ◽  
Vol 78 (3) ◽  
pp. 1468-1475 ◽  
Author(s):  
N. E. Schoppa ◽  
G. L. Westbrook
Keyword(s):  
Olfactory Bulb ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Mitral Cells ◽  
Group Iii ◽  
Metabotropic Glutamate ◽  
Selective Agonist ◽  
Group I ◽  
Mepsc Frequency ◽  
Group Ii

Schoppa, N. E. and G. L. Westbrook. Modulation of mEPSCs in olfactory bulb mitral cells by metabotropic glutamate receptors. J. Neurophysiol. 78: 1468–1475, 1997. Olfactory bulb mitral cells express group I (mGluR1), group II (mGluR2), and group III (mGluR7 and mGluR8) metabotropic glutamate receptors. We examined the role of these mGluRs on excitatory synaptic transmission in cultured mitral cells with the use of whole cell patch-clamp recordings. The effects of group-selective mGluR agonists and antagonists were tested on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-receptor-mediated miniature excitatory postsynaptic currents (mEPSCs). (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylate (ACPD) or the group-I-selective agonist 3,5-dihydroxyphenylglycine evoked an inward current accompanied by a decrease in membrane conductance, consistent with the previously described closure of potassium channels by group I agonists. The increased cellular excitability was accompanied by an increase in mEPSC frequency in some cells. When calcium entry was blocked by cadmium, ACPD or the group-II-selective agonist 2-(2,3-dicarboxycyclopropyl)-glycine reduced the mEPSC frequency. l-2-amino-4-phosphonobutyric acid (l-AP4), a group-III-selective agonist, caused a similar decrease. The concentration-dependence ofl-AP4-mediated inhibition was most consistent with activation of mGluR8. We investigated two possible effector mechanisms for the group III presynaptic receptor. Bath application of forskolin or 3-isobutyl-1-methylxantine had no effect on mEPSC frequency. Increasing calcium influx by raising extracellular K+ caused a large increase in the mEPSC frequency but did not enhance l-AP4-mediated inhibition. Thus inhibition of mEPSCs involves a mechanism downstream of calcium entry and appears to be independent of adenosine 3′,5′-cyclic monophosphate. Our results indicate that both group II and III receptors can inhibit glutamate release at mitral cell terminals. Although group II/III receptors had a similar effect on mEPSCs, differences in location on nerve terminals and in glutamate sensitivity suggest that each mGluR may have discrete actions on mitral cell activity.

Differential Changes of Group II and Group III mGluR Function in Central Amygdala Neurons in a Model of Arthritic Pain

2006 ◽  
Vol 96 (4) ◽  
pp. 1803-1815 ◽  
Author(s):  
Weidong Li ◽  
Volker Neugebauer
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Central Nucleus ◽  
Noxious Stimulation ◽  
Adult Rats ◽  
Group Iii ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Group Ii ◽  
Joint Arthritis ◽  
Stimulation Of

Metabotropic glutamate receptors (mGluRs) play important roles in neuroplasticity and disorders such as persistent pain. Group I mGluRs contribute to pain-related sensitization and synaptic plasticity of neurons in the laterocapsular division of the central nucleus of the amygdala (CeLC), although the roles of groups II and III mGluRs are not known. Extracellular single-unit recordings were made from 60 CeLC neurons in anesthetized adult rats. Background activity and evoked responses were measured before and during the development of the kaolin/carrageenan-induced knee-joint arthritis. Drugs were administered into the CeLC by microdialysis before and/or after arthritis induction. A selective group III mGluR agonist (LAP4) inhibited CeLC neurons' responses to stimulation of the knee and ankle in arthritis ( n = 7) more potently than under normal conditions ( n = 14). A selective group II agonist (LY354740) inhibited responses under normal conditions ( n = 12) and became more potent in inhibiting responses to noxious stimulation of the knee in arthritis ( n = 10). The effect of LY354740 on innocuous stimulation of the knee and stimulation of the ankle did not change in arthritis. Antagonists for groups II (EGLU, n = 9) and III (UBP1112, n = 8) had no effects under normal conditions. In arthritis, UPB1112 ( n = 5) facilitated the responses to stimulation of knee and ankle, whereas EGLU ( n = 5) selectively increased the responses to stimulation of the knee. These data suggest that mGluRs of groups II and III can inhibit nociceptive processing in CeLC neurons. The increased function and endogenous activation of group II mGluRs in the arthritis pain model appear more input-selective than the general changes of group III mGluRs.

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