Kaitocephalin antagonism of glutamate receptors expressed in xenopus oocytes

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.