Effect of choleretics on canalicular transport of protoporphyrin in the rat liver.
The major route of protoporphyrin elimination is biliary secretion. To clarify the nature of the secretory process, maximal canalicular secretion of protoporphyrin was determined under basal conditions and after treatment with various choleretics. The maximal secretion of protoporphyrin under basal conditions was 0.07 +/- 0.01 micrograms.min-1.100 g body wt-1. Infusion of physiological amounts of sodium taurocholate increased protoporphyrin secretion 13-fold (0.90 +/- 0.02), primarily by increasing the biliary protoporphyrin concentration. Biliary protoporphyrin secretion tended to plateau in spite of a continued rise in both biliary bile acid secretion and concentration. Infusion of sodium dehydrocholate increased protoporphyrin secretion, but to only 35% of that achieved by sodium taurocholate. Ethacrynic acid and phenobarbital increased bile flow over controls but failed to enhance protoporphyrin transport. Thus, canalicular secretion of protoporphyrin was maximally enhanced by micelle-forming bile acids and unaffected by nonbile acid choleretics. The observed limitation of protoporphyrin secretion may be related to achievement of a canalicular transport maximum or to a toxic effect of protoporphyrin on the transport process.
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D001652:Bile Ducts / Q000378:metabolism*; D003685:Dehydrocholic Acid / Q000494:pharmacology; D004976:Ethacrynic Acid / Q000494:pharmacology; D008099:Liver / Q000502:physiology*; D010477:Perfusion; D010634:Phenobarbital / Q000494:pharmacology; D011166:Porphyrins / Q000378:metabolism*; D011524:Protoporphyrins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000494:pharmacology
D011166:Porphyrins; D011524:Protoporphyrins; D013656:Taurocholic Acid; D004976:Ethacrynic Acid; D003685:Dehydrocholic Acid; D010634:Phenobarbital