Cantharidin poisoning associated with specific binding site in liver

Cantharidin, the potent vesicant and toxicant of blister beetles, was prepared as a radioligand to probe its mechanism of action. 3H]Cantharidin interacts in a saturable and specific manner with a binding site in mouse liver cytosol with apparent Kd and Bmax values of 30 nM and 1.8 pmol/mg protein, respectively. Comparisons of cantharidic acid, the related herbicide endothal, and 20 other oxabicycloheptane-dicarboxylic acids show that their potency as inhibitors of 3H]cantharidin binding is closely correlated with their intraperitoneal toxicity to mice. This binding site is also inhibited in vivo by toxic doses of cantharidin. The 3H]cantharidin binding site in mouse liver cytosol therefore represents, or serves as a model for, the site of toxic action of cantharidin and structurally-related compounds.