Conantokin-G: A novel peptide antagonist to the acid (NMDA) receptor

Mena, E. Edward; Gullak, Mary F.; Pagnozzi, Martin J.; Richter, Karl E.G.; Rivier, Jean; Cruz, Lourdes J.; Olivera, Baldomero M.

doi:10.1016/0304-3940(90)90637-o

Cited by 84 publications

(50 citation statements)

References 13 publications

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“…1) It is possible that Con G, which contains a glycine in position 2, could interfere with the glycine co-agonist binding site on the NR1 subunit. This interaction might then decrease the decay time constant as the affinity for glutamate might be reduced for NMDA receptors in the presence of Con G. Such allosteric interactions between the Con G and glycine binding sites have been reported (Donevan and McCabe 2000;Hammerland et al 1992;Mena et al 1990).…”

Section: Discussionmentioning

confidence: 85%

“…An earlier report indicates that Con G enhances strychnine-insensitive [ 3 H] glycine binding to rat forebrain membranes in a concentration-dependent manner (Mena et al 1990). Moreover, there is ample evidence suggesting allosteric interactions between ligands binding at the NMDA and glycine recognition sites (Danyz and Parsons 1998;Lester et al 1993;McBain and Mayer 1994;Priestley and Kemp 1994;Priestley et al 1996).…”

Section: Introductionmentioning

confidence: 99%

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Effect of Conantokin G on NMDA Receptor–Mediated Spontaneous EPSCs in Cultured Cortical Neurons

Alex¹,

Baucum²,

Wilcox³

2006

Journal of Neurophysiology

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. Effect of Conantokin G on NMDA receptor-mediated spontaneous EPSCs in cultured cortical neurons. J Neurophysiol 96: 1084 -1092. First published June 7, 2006 doi:10.1152/jn.01325.2005. Conantokin G (Con G), derived from the venom of Conus geographus, is the most characterized natural peptide antagonist targeted to N-methyl-D-aspartate (NMDA) receptors. Although Con G is known to bind to the glutamate binding site on the NR2 subunit of the receptor, it is unclear whether it can allosterically modulate the function of the receptor through the glycine binding site on the NR1 subunit. This study was designed to evaluate the action of Con G on NMDA receptormediated spontaneous excitatory postsynaptic currents (sEPSCs) and its modulation by glycine in cultured cortical neurons (13-19 days in vitro) using the whole cell patch-clamp technique. Con G inhibited NMDA receptor-mediated sEPSCs in a concentration-dependent manner. Also, the potency of Con G decreased as a function of time in culture. The inhibition of EPSCs observed after application of Con G in the presence of high (10 M) and nominal (no added) concentrations of glycine was not different at 13 days in vitro (DIV). Furthermore, similar results were obtained with experiments on Con G-induced inhibition of NMDA-evoked whole cell currents. These results indicate that glycine concentrations do not have a direct effect on Con G-induced inhibition of NMDA currents. In addition, age dependency in the action of Con G on cortical neurons in vitro suggests that this model system would be useful in examining the effects of different agonists/antagonists on native synaptic NMDA receptors.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Effect of Conantokin G on NMDA Receptor–Mediated Spontaneous EPSCs in Cultured Cortical Neurons

Alex¹,

Baucum²,

Wilcox³

2006

Journal of Neurophysiology

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“…2 Conantokins were first identified by their ability to cause sleep in young mice and hyperactivity in older mice when injected intracranially (1,2). Subsequently, they were characterized as antagonists of the N-methyl-D-aspartate (NMDA) receptor class of ionotropic glutamate receptors (3)(4)(5). The first conantokin peptide purified from the venom of Conus geographus, conantokin-G (con-G), was reported over 20 years ago (1).…”

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confidence: 99%

Novel Conantokins from Conus parius Venom Are Specific Antagonists of N-Methyl-D-aspartate Receptors

Teichert

Jimenéz

Twede

et al. 2007

Journal of Biological Chemistry

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“…При обработке неонатальных препаратов мозжечка крысы конантокином-G было показано, что последующее добавление NMDA не приводит к увеличению концентрации cGMP, в то же время обработка конантокином-G не влияла на функционирование каинатных рецепторов [138]. Исследование молекулярной специфичности конантокина-G показало, что этот токсин, действуя в субмикромолярных концентрациях, специфически связывается с NR2В-субъединицей NMDA-рецептора [2], но при этом не оказывает никакого эффекта на рецепторы, содержащие NR2А-субъединицу, даже при концентрации 50 мкМ [139].…”

Section: другие семейства конопептидов взаимодействующие с лигандзавunclassified

Conotoxins: from the biodiversity of gastropods to new drugs

et al. 2013

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A review describes general trends in research of conotoxins that are peptide toxins isolated from sea gastropods of the Conus genus, since the toxins were discovered in 1970 . There are disclosed a conotoxin classification, their structure diversity and different ways of action to their molecular targets, mainly, ion channels. In the applied aspect of conotoxin research, drug discovery and development is discussed, the drugs being based on conotoxin structure. A first exemplary drug is a ziconotide, which is an analgesic of new generation.

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Conantokin-G: A novel peptide antagonist to the acid (NMDA) receptor

Cited by 84 publications

References 13 publications

Effect of Conantokin G on NMDA Receptor–Mediated Spontaneous EPSCs in Cultured Cortical Neurons

Effect of Conantokin G on NMDA Receptor–Mediated Spontaneous EPSCs in Cultured Cortical Neurons

Novel Conantokins from Conus parius Venom Are Specific Antagonists of N-Methyl-D-aspartate Receptors

Conotoxins: from the biodiversity of gastropods to new drugs

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