CHARACTERIZATION OF A NOVEL CA2-PHENOL) AND ITS EFFECTS ON INTRACELLULAR CA2+ MOBILIZATION( PUMP INHIBITOR (BIS)

Bis-phenol, a phenolic antioxidant, is an inhibitor of sarcoplasmic re ticulum (SR), endoplasmic reticulum (ER) and plasma membrane Ca2+ ATPa ses. The concentration of bis-phenol giving half-maximal inhibition of the SR Ca2+-ATPase is 2 mu M. On binding to the SR Ca2+-ATPase it shi fts the E(2) to E(1) transition towards the E(2) state and slows the t ransition between E(2) to E(1). Bis-phenol completely inhibits Ca2+-de pendent ATP hydrolysis and Ca2+ uptake by rat cerebellar microsomes at a concentration of 30 mu M. The plasma membrane Ca2+-ATPase is also c ompletely inhibited at similar concentrations, however, the Na+/K+-ATP ase is only marginally affected. Other inhibitors of the ER Ca2+-ATPas es, thapsigargin and 2,5-di-(tert-butyl)-1,4-benzohydroquinone (BHQ), inhibit Ca2+ uptake by approximately 75%. Bis-phenol therefore inhibit s ah types of ER Ca2+-ATPases present in cerebellum. This inhibitor is also able to mobilize Ca2+ from intracellular Ca2+ stores, including those sensitive to InsP(3), in intact HL-60 cells.