Influence of drugs and chemicals upon hepatic enzymes and proteins. II. The effects of various barbiturates on the induction and reduction of hepatic cytoplasmic organic anion-binding proteins
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The effects of seven barbiturates (phenobarbital, three N-phenylbarbiturates and three N-cyclohexylbarbiturates) on the hepatic cytoplasmic organic anion-binding proteins, Y and Z, were investigated in an attempt to observe the structure-activity relationship of baributrates to induction and reduction of these two proteins. Sulfobromophthalein (BSP) was fully bound by the Y and Z proteins at ten minutes of mixing with the 10,5000 X g supernate. In low concentrations of BSP, saturation of binding of BSP by the Z protein was very low, and with increasing concentration, BSP-binding by the Z protein increased rapidly. The Y protein bound BSP sufficiently even in low concentrations of the dye. BSP-binding capacity of the Y protein was increased by phenobarbital, phetharbital and bucolome, and decreased by one of the N-phenylbarbiturates. BSP-binding capacity of the Z protein tended to be decreased by phenobarbital and phetharbital, but to be increased by bucolome. The other N-phenyl and N-cyclohexylbarbiturates had no effect on the binding capacities of the two proteins. From these results, it was concluded that the regulation by the barbiturates of cytoplasmic proteins is different from that of the microsomal enzymes, and that both type and structural relation are important in the induction and reduction of the Y and Z proteins.
Key wordsbarbiturates organic anion-binding proteins Y protein ligandin Z protein sulfobromophthalein
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