scholarly journals Expression and Cell Distribution of Group I and Group II Metabotropic Glutamate Receptor Subtypes in Taylor-type Focal Cortical Dysplasia

Epilepsia ◽  
2003 ◽  
Vol 44 (6) ◽  
pp. 785-795 ◽  
Author(s):  
Eleonora Aronica ◽  
Jan A. Gorter ◽  
Gerard H. Jansen ◽  
Cees W. M. Van Veelen ◽  
Peter C. Van Rijen ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Focal Cortical Dysplasia ◽  
Cortical Dysplasia ◽  
Receptor Subtypes ◽  
Cell Distribution ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Group Ii

Roles of specific metabotropic glutamate receptor subtypes in regulation of hippocampal CA1 pyramidal cell excitability

1995 ◽  
Vol 74 (1) ◽  
pp. 122-129 ◽  
Author(s):  
R. W. Gereau ◽  
P. J. Conn
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Brain Slices ◽  
Second Messenger ◽  
Receptor Subtypes ◽  
Bhk Cells ◽  
Group Iii ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Group Ii

1. Metabotropic glutamate receptors (mGluRs) are coupled to various second-messenger systems through guanosine 5'-triphosphate-binding proteins. To date, at least seven mGluRs have been cloned, and these mGluR subtypes can be divided into three major groups on the basis of similarities in amino acid sequence, coupling to second-messenger cascades in expression systems, and pharmacological profiles. These groups include group I (mGluR1 and mGluR5), group II (mGluR2 and mGluR3), and group III (mGluR4, mGluR6, and mGluR7). 2. On the basis of its selective activation of phosphoinositide hydrolysis in brain slices and its ability to activate mGluR1a expressed in Xenopus oocytes, others have suggested that 3.5-dihydroxyphenylglycine (DHPG) may be selective for group I mGluRs. Consistent with this hypothesis, we report that DHPG also activates mGluR5 expressed in oocytes, whereas it is inactive at mGluR4 and mGluR7 expressed in baby hamster kidney (BHK) cells. The compound (2S,1'R,2'R,3'R)-2-(2.3-dicarboxycyclopropyl)glycine (DCG-IV) activates both mGluR2 and mGluR3 at submicromolar concentrations, whereas it is inactive at mGluR4 and mGluR1, suggesting that this compound may be selective for group II mGluRs. Consistent with this hypothesis, we find that DCG-IV does not activate mGluR5 expressed in oocytes and does not activate mGluR7 expressed in BHK cells. These findings suggest that DHPG and DCG-IV are highly selective agonists for group I and group II mGluRs, respectively. 3. Previous studies that have examined the physiological roles of mGluRs have generally used agonists that do not differentiate between the various subtypes.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential Effects of Metabotropic Glutamate Receptor Antagonists on Bursting Activity in the Amygdala

1999 ◽  
Vol 81 (5) ◽  
pp. 2056-2065 ◽  
Author(s):  
N. Bradley Keele ◽  
Volker Neugebauer ◽  
Patricia Shinnick-Gallagher
Keyword(s):  
Glutamate Receptor ◽  
Stimulus Intensity ◽  
Metabotropic Glutamate Receptor ◽  
Receptor Antagonists ◽  
Differential Effects ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Glutamate Receptor Antagonists ◽  
Group Ii ◽  
Bursting Activity

Differential effects of metabotropic glutamate receptor antagonists on bursting activity in the amygdala. Metabotropic glutamate receptors (mGluRs) are implicated in both the activation and inhibition of epileptiform bursting activity in seizure models. We examined the role of mGluR agonists and antagonists on bursting in vitro with whole cell recordings from neurons in the basolateral amygdala (BLA) of amygdala-kindled rats. The broad-spectrum mGluR agonist 1 S,3 R-1-aminocyclopentane dicarboxylate (1 S,3 R-ACPD, 100 μM) and the group I mGluR agonist ( S)-3,5-dihydroxyphenylglycine (DHPG, 20 μM) evoked bursting in BLA neurons from amygdala-kindled rats but not in control neurons. Neither the group II agonist (2 S,3 S,4 S)-α-(carboxycyclopropyl)-glycine (l-CCG-I, 10 μM) nor the group III agonistl-2-amino-4-phosphonobutyrate (l-AP4, 100 μM) evoked bursting. The agonist-induced bursting was inhibited by the mGluR1 antagonists (+)-α-methyl-4-carboxyphenylglycine [(+)-MCPG, 500 μM] and ( S)-4-carboxy-3-hydroxyphenylglycine [( S)-4C3HPG, 300 μM]. Kindling enhanced synaptic strength from the lateral amygdala (LA) to the BLA, resulting in synaptically driven bursts at low stimulus intensity. Bursting was abolished by (S)-4C3HPG. Further increasing stimulus intensity in the presence of ( S)-4C3HPG (300 μM) evoked action potential firing similar to control neurons but did not induce epileptiform bursting. In kindled rats, the same threshold stimulation that evoked epileptiform bursting in the absence of drugs elicited excitatory postsynaptic potentials in ( S)-4C3HPG. In contrast (+)-MCPG had no effect on afferent-evoked bursting in kindled neurons. Because (+)-MCPG is a mGluR2 antagonist, whereas ( S)-4C3HPG is a mGluR2 agonist, the different effects of these compounds suggest that mGluR2 activation decreases excitability. Together these data suggest that group I mGluRs may facilitate and group II mGluRs may attenuate epileptiform bursting observed in kindled rats. The mixed agonist–antagonist ( S)-4C3HPG restored synaptic transmission to control levels at the LA-BLA synapse in kindled animals. The different actions of ( S)-4C3HPG and (+)-MCPG on LA-evoked bursting suggests that the mGluR1 antagonist–mGluR2 agonist properties may be the distinctive pharmacology necessary for future anticonvulsant compounds.

β-NAAG Rescues LTP From Blockade by NAAG in Rat Dentate Gyrus via the Type 3 Metabotropic Glutamate Receptor

2001 ◽  
Vol 85 (3) ◽  
pp. 1097-1106 ◽  
Author(s):  
Paul M. Lea IV ◽  
Barbara Wroblewska ◽  
John M. Sarvey ◽  
Joseph H. Neale
Keyword(s):  
Dentate Gyrus ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Granule Cells ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Group Ii ◽  
Type 3 ◽  
Mglur Antagonist ◽  
In Cells

N-Acetylaspartylglutamate (NAAG) is an agonist at the type 3 metabotropic glutamate receptor (mGluR3), which is coupled to a Gi/o protein. When activated, the mGluR3 receptor inhibits adenylyl cyclase and reduces the cAMP-mediated second-messenger cascade. Long-term potentiation (LTP) in the medial perforant path (MPP) of the hippocampal dentate gyrus requires increases in cAMP. The presence of mGluR3 receptors and NAAG in neurons of the dentate gyrus suggests that this peptide transmitter may inhibit LTP in the dentate gyrus. High-frequency stimulation (100 Hz; 2 s) of the MPP resulted in LTP of extracellularly recorded excitatory postsynaptic potentials at the MPP-granule cell synapse of rat hippocampal slices. Perfusion of the slice with NAAG (50 and 200 μM) blocked LTP. Neither 50 nor 200 μM NAAG produced N-methyl-d-aspartate receptor currents in the granule cells of the acute hippocampal slice. The group II mGluR antagonist ethyl glutamate (100 μM) and a structural analogue of NAAG, β-NAAG (100 μM), prevented the blockade of LTP by NAAG. Paired-pulse depression of the excitatory postsynaptic potential at 20- and 80-ms interpulse intervals (IPI) was not affected by NAAG or β-NAAG. β-NAAG did not affect inositol trisphosphate production stimulated by the agonist glutamate in cells expressing the group I mGluR1α or mGluR5. β-NAAG blocked the decrease in forskolin-stimulated cAMP by the group II mGluR agonist (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine (DCG-IV) but not the group III mGluR agonist L(+)-2-amino-4-phosphonobutyric acid in cerebellar granule cells. In cells transfected with mGluR3, but not mGluR2, β-NAAG blocked forskolin-stimulated cAMP responses to glutamate, NAAG, the nonspecific group I, II agonist trans-ACPD, and the group II agonist DCG-IV. We conclude that β-NAAG is a selective mGluR antagonist capable of differentiating between mGluR2 and mGluR3 subtypes and that the mGluR3 receptor functions to regulate activity-dependent synaptic potentiation in the hippocampus.

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