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 (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 similar to 100 mu M) and of metabotropic (IC50 > 100 mu M) glutamate receptors expressed by rat brain mRNA.