Kaitocephalin antagonism of glutamate receptors expressed in xenopus oocytes

Agenor Limon; Jorge M. Reyes-Ruiz; Rishi G. Vaswani; A. Richard Chamberlin; Ricardo Miledi

doi:10.1021/cn900037c

Kaitocephalin antagonism of glutamate receptors expressed in xenopus oocytes

Agenor Limon, Jorge M. Reyes-Ruiz, Rishi G. Vaswani, A. Richard Chamberlin, Ricardo Miledi

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

Kaitocephalin is the first discovered natural toxin with protective properties against excitotoxic death of cultured neurons induced by N-methyl-d-aspartate (NMDA) or -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainic acid (kainate, KA) receptors. Nevertheless, the effects of kaitocephalin on the function of these receptors were unknown. In this work, we report some pharmacological properties of synthetic (-)-kaitocephalin on rat brain glutamate receptors expressed in Xenopus laevis oocytes and on the homomeric AMPA-type GluR3 and KA-type GluR6 receptors. Kaitocephalin was found to be a more potent antagonist of NMDA receptors (IC₅₀ = 75 ± 9 nM) than of AMPA receptors from cerebral cortex (IC₅₀ = 242 ± 37 nM) and from homomeric GluR3 subunits (IC₅₀ = 502 ± 55 nM). Moreover, kaitocephalin is a weak antagonist of the KA-type receptor GluR6 (IC₅₀ 100 M) and of metabotropic (IC₅₀ > 100 M) glutamate receptors expressed by rat brain mRNA.

Original language	English (US)
Pages (from-to)	175-181
Number of pages	7
Journal	ACS chemical neuroscience
Volume	1
Issue number	3
DOIs	https://doi.org/10.1021/cn900037c
State	Published - Mar 17 2010
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Physiology
Cognitive Neuroscience
Cell Biology

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abstract = "Kaitocephalin is the first discovered natural toxin with protective properties against excitotoxic death of cultured neurons induced by N-methyl-d-aspartate (NMDA) or -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainic acid (kainate, KA) receptors. Nevertheless, the effects of kaitocephalin on the function of these receptors were unknown. In this work, we report some pharmacological properties of synthetic (-)-kaitocephalin on rat brain glutamate receptors expressed in Xenopus laevis oocytes and on the homomeric AMPA-type GluR3 and KA-type GluR6 receptors. Kaitocephalin was found to be a more potent antagonist of NMDA receptors (IC50 = 75 ± 9 nM) than of AMPA receptors from cerebral cortex (IC50 = 242 ± 37 nM) and from homomeric GluR3 subunits (IC50 = 502 ± 55 nM). Moreover, kaitocephalin is a weak antagonist of the KA-type receptor GluR6 (IC50 100 M) and of metabotropic (IC50 > 100 M) glutamate receptors expressed by rat brain mRNA.",

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AU - Limon, Agenor

AU - Reyes-Ruiz, Jorge M.

AU - Vaswani, Rishi G.

AU - Chamberlin, A. Richard

AU - Miledi, Ricardo

PY - 2010/3/17

Y1 - 2010/3/17

N2 - Kaitocephalin is the first discovered natural toxin with protective properties against excitotoxic death of cultured neurons induced by N-methyl-d-aspartate (NMDA) or -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainic acid (kainate, KA) receptors. Nevertheless, the effects of kaitocephalin on the function of these receptors were unknown. In this work, we report some pharmacological properties of synthetic (-)-kaitocephalin on rat brain glutamate receptors expressed in Xenopus laevis oocytes and on the homomeric AMPA-type GluR3 and KA-type GluR6 receptors. Kaitocephalin was found to be a more potent antagonist of NMDA receptors (IC50 = 75 ± 9 nM) than of AMPA receptors from cerebral cortex (IC50 = 242 ± 37 nM) and from homomeric GluR3 subunits (IC50 = 502 ± 55 nM). Moreover, kaitocephalin is a weak antagonist of the KA-type receptor GluR6 (IC50 100 M) and of metabotropic (IC50 > 100 M) glutamate receptors expressed by rat brain mRNA.

AB - Kaitocephalin is the first discovered natural toxin with protective properties against excitotoxic death of cultured neurons induced by N-methyl-d-aspartate (NMDA) or -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainic acid (kainate, KA) receptors. Nevertheless, the effects of kaitocephalin on the function of these receptors were unknown. In this work, we report some pharmacological properties of synthetic (-)-kaitocephalin on rat brain glutamate receptors expressed in Xenopus laevis oocytes and on the homomeric AMPA-type GluR3 and KA-type GluR6 receptors. Kaitocephalin was found to be a more potent antagonist of NMDA receptors (IC50 = 75 ± 9 nM) than of AMPA receptors from cerebral cortex (IC50 = 242 ± 37 nM) and from homomeric GluR3 subunits (IC50 = 502 ± 55 nM). Moreover, kaitocephalin is a weak antagonist of the KA-type receptor GluR6 (IC50 100 M) and of metabotropic (IC50 > 100 M) glutamate receptors expressed by rat brain mRNA.

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Kaitocephalin antagonism of glutamate receptors expressed in xenopus oocytes

Abstract

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