Effects of chlorpromazine on taurocholate transport in isolated rat hepatocytes.
Chlorpromazine has been shown to have no effect on the uptake of the endogenous bile salt substrate, taurocholate, by isolated rat hepatocytes. It has been shown, however, to inhibit directly release of taurocholate from pre-loaded cells over extended incubation. However, there was no inhibition of the efflux process per se as shown by similar initial rates of taurocholate efflux in the presence or absence of chlorpromazine. Pretreatment of rats with chlorpromazine (100 mumoles/kg) resulted in no change in the ability to transport (that is, accumulate or secrete) taurocholate by hepatocytes isolated 2, 24, 36, 48, or 60 hr later. The data indicate that, if a direct effect on bile acid transport is important in chlorpromazine induced biliary dysfunction, then it involves release rather than uptake at the cell membrane. However, as efflux itself is not inhibited chlorpromazine may interfere with release of taurocholate from intracellular sites.
Stacey
N H
NH
National Institute of Occupational Health and Safety, University of Sydney, N.S.W., Australia.
D000818:Animals; D002478:Cells, Cultured; D002746:Chlorpromazine / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000378:metabolism*
D013656:Taurocholic Acid; D002746:Chlorpromazine