Competition of pravastatin and dibromosulfophthalein on the electroneutral and electrogenic tetrabromosulfophthalein uptake in rat liver.
The effect of pravastatin (PVST) and dibromosulfophthalein (DBSP) on the hepatic uptake of bromosulfophthalein (BSP) was investigated in liver plasma membrane vesicles enriched on basolateral fraction. BSP uptake was measured either in the absence (electroneutral component) or in the presence of a membrane potential (electrogenic component). PVST and DBSP inhibited both components of BSP uptake. The Dixon and Cornish-Bowden plot of the data revealed a competitive type of inhibition for PVST and DBSP on the electroneutral portion of BSP uptake. The inhibition constants (K(i), mM) were 0.650+/-0.050 for PVST and 0.020+/-0.005 for DBSP. These data indicate that PVST, DBSP and BSP share a common electroneutral transport system at basolateral liver plasma membrane. On the contrary, PVST exerted a non-competitive type of inhibition on the electrogenic component of BSP uptake (K(i)=0.210+/-0.040 mM) and DBSP produced a mixed type of inhibition (K(i)=0.018+/-0.002 mM). These results indicate that PVST does not compete with the electrogenic BSP carrier system at the level of the substrate binding site but modulates its functionality and that DBSP shares the electrogenic component of BSP transport and also modulates the performance of this carrier system.
Farmacología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, CONICET, Suipacha 531, 2000, Rosario, Argentina
A M.
AM
Torres