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 alpha-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 (IC(50) = 75 +/- 9 nM) than of AMPA receptors from cerebral cortex (IC(50) = 242 +/- 37 nM) and from homomeric GluR3 subunits (IC(50) = 502 +/- 55 nM). Moreover, kaitocephalin is a weak antagonist of the KA-type receptor GluR6 (IC(50) ~ 100 muM) and of metabotropic (IC(50) > 100 muM) glutamate receptors expressed by rat brain mRNA.