2,5-Di(tert-butyl)-1,4-benzohydroquinone - a novel inhibitor of liver microsomal Ca²⁺ sequestration

Treatment of rat liver microsomes with 2,5-di(tert-butyl)-1,4-benzohydroquinone caused a dose-related inhibition (K_i{reversed tilde equals}1 μM) of ATP-dependent Ca²⁺ sequestration. This was paralleled by a similar impairment of the microsomal Ca²⁺ -stimulated ATPase activity. In contrast, the hydroquinone failed to induce Ca²⁺ release from Ca²⁺ -loaded liver mitochondria (supplied with ATP), and inhibited neither the mitochondrial F₁F₀-ATPase nor the Ca²⁺ -stimulated ATPase activity of the hepatic plasma membrane fraction. The inhibition of microsomal Ca²⁺ sequestration was not associated with any apparent alteration of membrane permeability or loss of other microsomal enzyme activities or modification of microsomal protein thiols. These findings suggest that 2,5-di(tert-butyl)-1,4-benzohydroquinone is a potent and selective inhibitor of liver microsomal Ca²⁺ sequestration which may be a useful tool in studies of Ca²⁺ fluxes in intact cells and tissues.