Partial characterization of specific cantharidin binding sites in mouse tissues

摘要: The mode of action cantharidin, the natural vesicant blister beetles, is examined by radioligand binding studies with mouse tissues. [3H]Cantharidin undergoes specific and saturable liver cytosol, which characterized as follows: Kd Bmax values 30 nM 1.8 pmol/mg protein, respectively; linearity respect to protein concentration; pH optimum 6.5 7.5; association dissociation half-times 20 min 12 hr, 50% inhibition Mg2+ at 70 microM, Ca2+ 224 pyrophosphate 27 nucleotide triphosphates 52-81 microM. site a loss activity 45 degrees or higher. toxicological relevance this [3H]cantharidin cytosol established in three ways. First, potency 15 active cantharidin analogs for inhibiting correlated their acute toxicity mice (r = 0.829). Second, 26 related compounds that are inactive also little no mice. Finally, [3H] from poisoned increasing amounts unlabeled inhibited dose-dependent manner. specifically binds fractions blood, brain, heart, kidney, lung, pancreas, skin, spleen, stomach. characteristics brain very similar those determined Kd, Bmax, association/dissociation kinetics, sensitivity inhibitors. It therefore appears oxabicycloheptanes, including herbicide endothal, attributable possibly other