Identification of Carrier Proteins in Hepatocytes by (Photo) Affinity Labels Derived from Foreign Cyclopeptides
Certain cyclopeptides of toxicological (e.g. phallotoxins) or pharmacological interest (e.g. antamanide, cyclosomatostatins) are rapidly eliminated via the biliary pathway (Frimmer 1987, Caldwell 1984). A liver-specific clearance mechanism is responsible for the hepatospecific toxic effects of e.g. phallotoxins and for the short half life of cyclosomatostatins. We did not expect a carrier-mediated uptake to be responsible for this first-pass elimination. The transport of various cyclopeptides is driven by a sodium gradient and the membrane potential (Review by Frimmer and Ziegler 1988). By mutual competition experiments it became evident that bile acids are the physiological substrates of this transport system. Actually, the carrier seems to be unable to discriminate between various structurally different compounds like bile acids and cyclopeptides. It was therefore termed a “multispecific transporter” (Ziegler et al. 1985).
KeywordsEnzymatic Degradation Half Life Cyclosporin Choline Photolysis
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