Chlorpromazine, administered in vivo and in vitro, inhibits the efflux of bile acids in freshly isolated rat hepatocytes.
Although it has been speculated that chlorpromazine may alter the transhepatic movement of bile acids from plasma to bile, the effect of chlorpromazine on various determinants of bile acid transport in isolated rat hepatocytes remains incompletely defined. In particular, there is little information about the effect of chlorpromazine on the release of bile acids from freshly isolated hepatocytes. Therefore, we examined the effect of chlorpromazine, administered in vivo and in vitro, on the efflux rate of radiolabeled bile acids in freshly isolated rat hepatocytes. In an isolated haptocyte system, it is not possible to distinguish the sinusoidal plasma membrane function of efflux (back diffusion) from the canalicular plasma membrane function of excretion. Therefore, efflux, as used in this manuscript, reflects both back diffusion and excretion. In vitro, chlorpromazine produced a rapid dose dependent significant (P less than 0.05) decrease of the bile acid efflux rate in freshly isolated hepatocytes. This decrease in bile acid efflux was observed at chlorpromazine concentrations which did not alter hepatocyte plasma membrane permeability (viability), as measured by intracellular potassium content, release of lactate dehydrogenase, and trypan blue exclusion. Moreover, in freshly isolated hepatocytes from chlorpromazine pretreated rats, a significant (P less than 0.05) decrease in the bile acid efflux rate was also observed, and this decrease in efflux was similar in magnitude to the decrease in bile acid efflux observed following exposure of freshly isolated hepatocytes to chlorpromazine in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, University of Washington, Seattle.
R A
RA
Willson
J R
JR
Hart
T
T
Hall
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002746:Chlorpromazine / Q000494:pharmacology*; D019826:Cholic Acid; D002793:Cholic Acids / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D006000:Glycocholic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000494:pharmacology; D013997:Time Factors
D001647:Bile Acids and Salts; D002793:Cholic Acids; D013656:Taurocholic Acid; D019826:Cholic Acid; D006000:Glycocholic Acid; D002746:Chlorpromazine