LY341495 is a nanomolar potent and selective antagonist of group II metabotropic glutamate receptors

Kingston, Anne; Ornstein, Paul L.; Wright, Rebecca A.; Johnson, Bryan G.; Mayne, N.G.; Burnett, J. Paul; Belagaje, Rama M.; Wu, Size; Schoepp, Darryle D.

doi:10.1016/s0028-3908(97)00191-3

Cited by 357 publications

(296 citation statements)

References 26 publications

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“…LY379268 is a highly selective mGlu2/3 agonist with 4100-fold selectivity over mGlu1, 5, 4, 7, and 8 Schoepp et al, 1999). Similarily, LY341495 is a nanomolar potent competitive antagonist for mGlu2/3 receptors with some selectivity against mGlu8 (10-fold) but much greater selectivity against the other mGlu receptors (Kingston et al, 1998;Schoepp et al, 1999). Thus, the maximally effective dose of LY379268 utilized here would, most likely, selectively activate the mGlu2 and 3 receptors and pretreatment with the antagonist LY341495 would be expected to partially prevent this mGlu2/3-mediated activity.…”

Section: In Situ Hybridizationmentioning

confidence: 76%

Group II Metabotropic Glutamate Receptor Modulation of DOI-induced c-fos mRNA and Excitatory Responses in the Cerebral Cortex

Zhai

George

Zhai

et al. 2003

Neuropsychopharmacol

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Recent studies have demonstrated that the hallucinogen 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) enhances glutamatergic transmission in the prefrontal cortex. This increase can be suppressed by metabotropic glutamate2/3 (mGlu2/3) receptor activation. In addition to enhancing glutamatergic transmission, DOI increases cortical c-fos expression. We tested if a reduction in glutamate release produced by mGlu2/3 receptor activation attenuates DOI-induced c-fos expression in the cortex. Similar to previous studies, DOI produced a robust increase in c-fos mRNA throughout the cortex, including the prefrontal, frontoparietal, and somatosensory regions. Pretreatment with the mGlu2/3 agonist LY379268 attenuated the DOI-induced increase in the prefrontal cortex. This suppression was blocked by the mGlu2/3 antagonist LY341495. In contrast, the DOI-induced increase in c-fos mRNA in the frontoparietal and somatosensory cortex was unaffected by the mGlu2/3 agents. These findings suggest that Group II metabotropic glutamate receptor agonists are capable of modulating postsynaptic function preferentially in the limbic cortex under conditions of enhanced glutamate release.

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Section: In Situ Hybridizationmentioning

confidence: 76%

Group II Metabotropic Glutamate Receptor Modulation of DOI-induced c-fos mRNA and Excitatory Responses in the Cerebral Cortex

Zhai

George

Zhai

et al. 2003

Neuropsychopharmacol

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“…1A). This LTD was completely blocked by bath application of the broad-spectrum mGluR antagonist LY341495 (10 M; 94.9 Ϯ 5.3%, n ϭ 5; p Ͻ 0.05) (21), suggesting that it is mediated by mGluR (Fig. 1B).…”

Section: Dhpg-induced An Mglur5-dependent Ltd-using Field Po-mentioning

confidence: 88%

Rap1-induced p38 Mitogen-activated Protein Kinase Activation Facilitates AMPA Receptor Trafficking via the GDI·Rab5 Complex

Huang

You

et al. 2004

Journal of Biological Chemistry

166

198

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Recent evidence has emphasized the importance of p38 mitogen-activated protein kinase (MAPK) in the induction of metabotropic glutamate receptor (mGluR)-dependent long term depression (LTD) at hippocampal CA3-CA1 synapses. However, the cascade responsible of mGluR to activate p38 MAPK and the signaling pathway immediately downstream from it to induce synaptic depression is poorly understood. Here, we show that transient activation of group I mGluR with the selective agonist (S)-3,5-dihydroxyphenylglycine (DHPG) activates p38 MAPK through G protein ␤␥-subunit, small GTPase Rap1, and MAPK kinase 3/6 (MKK3/6), thus resulting in mGluR5-dependent LTD. Furthermore, our data clearly show that an accelerating AMPA receptor endocytosis by stimulating the formation of guanyl nucleotide dissociation inhibitor-Rab5 complex is a potential downstream processing of p38 MAPK activation to mediate DHPG-LTD. These results suggest an important role for Rap1-MKK3/6-p38 MAPK pathway in the induction of mGluR-dependent LTD by directly coupling to receptor trafficking machineries to facilitate the loss of synaptic AMPA receptors.Long term depression (LTD) 1 is a persistent activity-dependent decrease of synaptic efficacy that together with the converse process, long term potentiation, has been considered to be crucial for information storage in the brain (1, 2). In the hippocampus, LTD is divided into three categories: homosynaptic, heterosynaptic, and associative LTD (3). The bestcharacterized form of homosynaptic LTD is induced in the CA1 region of the hippocampus by prolonged low frequency synaptic stimulation via a NMDA receptor-dependent rise in postsynaptic [Ca 2ϩ ] i and the activation of serine/threonine protein phosphatases (4). Recent work has shown that mechanistically distinct type of LTD can be induced in the CA1 region by other types of synaptic stimulation or brief pharmacological treatments. For example, a prolonged period of paired-pulse stimulation or a direct application of the selective group I mGluR agonists, such as DHPG, can induce a robust mGluR-dependent form of LTD that is independent of NMDA receptor activation (5). In contrast to the mechanisms of NMDA receptor-dependent LTD, which are fairly well established, the mechanisms of induction and the site of expression of mGluR-dependent LTD are still a matter of some considerable debate. Current studies have reported that the induction of mGluR-dependent LTD does not require extracellular Ca 2ϩ (6), Ca 2ϩ release from intracellular stores (7), activation of Ca 2ϩ /calmodulin-dependent protein kinase II (8), protein kinase A or protein kinase C (7, 9), or serine/ threonine protein phosphatases (9). However, this form of LTD requires activation of G q -type G proteins (10), a local translation of dendritic mRNA (5, 11), a long-lasting loss of postsynaptic AMPA receptors (12, 13), and activation of protein tyrosine phosphatases (14). In addition, more recent studies suggest that p38 MAPK signaling also serves as a signal mediator in the induction of mGluR-depende...

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“…LY341495 was from Tocris Cookson Ltd. (Bristol, UK). LY341495 is a highly selective group II mGluR antagonist (32). All compounds were dissolved in saline for i.p.…”

Section: Drugsmentioning

confidence: 99%

Phencyclidine and Dizocilpine Induced Behaviors Reduced by N-acetylaspartylglutamate Peptidase Inhibition via Metabotropic Glutamate Receptors

Olszewski

Wegorzewska

Monteiro

et al. 2008

Biological Psychiatry

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LY341495 is a nanomolar potent and selective antagonist of group II metabotropic glutamate receptors

Cited by 357 publications

References 26 publications

Group II Metabotropic Glutamate Receptor Modulation of DOI-induced c-fos mRNA and Excitatory Responses in the Cerebral Cortex

Group II Metabotropic Glutamate Receptor Modulation of DOI-induced c-fos mRNA and Excitatory Responses in the Cerebral Cortex

Rap1-induced p38 Mitogen-activated Protein Kinase Activation Facilitates AMPA Receptor Trafficking via the GDI·Rab5 Complex

Phencyclidine and Dizocilpine Induced Behaviors Reduced by N-acetylaspartylglutamate Peptidase Inhibition via Metabotropic Glutamate Receptors

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