DIFFERENT RELATIONSHIPS BETWEEN CELLULAR ATP AND HEPATIC-UPTAKE AMONGTAUROCHOLATE, CHOLATE, AND ORGANIC-ANIONS

Effects of cellular ATP content on uptake of cholate (CA) and organic anions (OAs; dibromosulfophthalein and benzylpenicillin) by isolated r at hepatocytes were investigated and were compared with that on tauroc holate (TCA). Within 5 min of exposure to metabolic inhibitors (MIs), cellular ATP content fell to less than one-fifth of the control value, and the initial velocity of the total uptake of CA, Na+-independent u ptake of CA and TCA, and the uptake of the OAs dropped in parallel wit h the decrease in cellular ATP. Whereas for the total uptake of TCA, t he initial uptake remained virtually unchanged for a 5-min incubation with the MIs; a significant decrease in uptake was observed only after longer incubation times. Under variously ATP-decreased conditions, th e initial velocity of the total uptake of CA and OAs was demonstrated to have a saturable relation to cellular ATP content, irrespective of exposure time to MIs. A difference in the Na+-dependent uptake of TCA and CA was also observed in terms of the inhibitory effect of the orga nic anion pravastatin. That is, the inhibition by pravastatin was part ial for TCA uptake but almost complete for CA uptake. These findings s uggest the following. 1) The mechanism of Na+-dependent CA uptake is d ifferent from that of TCA. 2) The Na+-independent uptake of bile acids and organic anions may be driven either by ATP hydrolysis (primary ac tive transport) or by an as yet unidentified ion gradient that dissipa tes more rapidly than the Na+ gradient.