New substrates of the multispecific bile acid transporter in liver cells: interference of some linear renin inhibiting peptides with transport protein(s) for bile acids.
Interactions between some stable linear peptides with renin inhibitory activity and a multispecific transport system in the basolateral plasma membrane of liver cells was studied on cell suspensions. The peptides used in our experiments were taken up by liver cells and subsequently eliminated without any biotransformation (e.g., proteolysis). No degradation products could be detected in the extracellular medium by thin-layer chromatography. All peptides tested inhibited the uptake of physiological and of some foreign substrates of the multispecific bile acid transporter (MT). The phalloidin response of liver cells was also inhibited to a similar degree in a concentration-dependent manner. The potency of inhibition did not correlate with the lipophilic properties of the peptides. On the other hand a tight correlation could be documented between the inhibition of cholate transport and that of the phalloidin response. Transport inhibition of typical substrates of the MT by the above renin inhibitors was competitive. In contrast, the transport of a typical substrate of the bilirubin carrier (rifampicin), of amino acids (alpha-aminoisobutyric acid), long chain fatty acids (oleic acid) and cationic compounds (thiamin hydrochloride) was not inhibited by the same renin inhibitors. These results indicate that linear renin inhibiting peptides are taken up into liver cells by carrier proteins related to the MT.
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Institut für Pharmakologie und Toxikologie, Justus-Liebig-Universität Giessen, F.R.G.
Ziegler
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K
D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001692:Biological Transport; D002793:Cholic Acids / Q000378:metabolism; D007458:Iodipamide / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010042:Ouabain / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D010590:Phalloidine / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D012293:Rifampin / Q000378:metabolism; D013448:Sulfobromophthalein / Q000378:metabolism; D013831:Thiamine / Q000378:metabolism; D000092502:Renin Inhibitors
D000621:Aminoisobutyric Acids; D001647:Bile Acids and Salts; D002793:Cholic Acids; D007458:Iodipamide; D019301:Oleic Acid; D009829:Oleic Acids; D010042:Ouabain; D010455:Peptides; D010590:Phalloidine; D012293:Rifampin; D013448:Sulfobromophthalein; D013831:Thiamine; D000092502:Renin Inhibitors