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.
Graziano
M J
MJ
Department of Entomological Sciences, University of California, Berkeley 94720.
Waterhouse
A L
AL
Casida
J E
JE
D000818:Animals; D001665:Binding Sites; D002193:Cantharidin / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity*; D055598:Chemical Phenomena; D002621:Chemistry; D003600:Cytosol / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D002193:Cantharidin