Summary
The uptake of iodipamide and of the cyclopeptide antamanide by isolated hepatocytes was reduced reversibly in the absence of oxygen as recently shown for the transport of cholate. Oligomycin, antimycin A and carbonylcyano-chlorophenylhydrazone (CCCP) completely blocked the uptake of iodipamide and antamanide whereas the uptake of cholate was only partially decreased. Reduction of ATP in hepatocytes following replacement of glucose by fructose inhibited the uptake of iodipamide, of antamanide, and also of cholate. In contrast, the penetration of bromosulfophthalein remained unaffected under the above conditions. Arrhenius analysis yielded high apparent activation energies for the uptake of cholate, iodipamide, and antamanide being 89, 77 and 55 kJ/mol respectively but only 22 kJ/mol for bromosulfophthalein.
Mutual transport inhibition was found for iodipamide, antamanide and cholate as well as for bromosulfophthalein. Cholate inhibited the uptake of iodipamide and antamanide competitively. In contrast, bromosulfophthalein inhibited iodipamide uptake in a mixed order fashion.
The results suggest a common uptake mechanism for cholate, iodipamide and antamanide different from that of bromosulfophthalein.
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References
Anwer MS, Hegner D (1978) Effect of organic anions on bile acid uptake by isolated rat hepatocytes. Hoppe-Seyler's Z Physiol Chem 359: 1027–1030
Anwer MS, Kroker R, Hegner D (1976) Cholic acid uptake into isolated rat hepatocytes. Hoppe-Seyler's Z Physiol Chem 357:1477–1486
Barany EH (1972) Inhibition by hippurate and probenacid of in vitro uptake of iodipamide and o-iodohippurate. A composite uptake system for iodipamide in chorioid plexus, kidney cortex anterior uvea of several species. Acta Physiol Scand 86:12–27
Berk RN, Loeb PM, Ellzey BA (1977) Contrast materials for intravenous cholangiography. In: Miller RE, Skucas J (eds) Radiographic contrast agents. University Park Press, Baltimore
Berry MS, Friend DS (1969) High-yield preparation of isolated rat liver parenchymal cells. J Cell Biol 43:506–529
Blom A, Keulemans K, Meijer DKF (1981) Transport of dibromosulphthalein by isolated rat hepatocytes. Biochem Pharmacol 30: 1809–1816
Brauer RW, Pessotti RL (1949) The removal of bromosulphthalein from blood plasma by the liver of the rat. J Pharm Exp Ther 97:357–370
Brauer RW, Pessotti RL (1950) Hepatic uptake and biliary excretion of bromsulphthalein in the dog. Am J Physiol 162:565–574
Burr R, Schwenk M, Pfaff E (1977a) Interaction of bromosulfophthalein with mitochondrial membranes: Inhibition of respiration. Biochem Pharmacol 26:461–466
Burr R, Schwenk M, Pfaff E (1977a) Interaction of bromosulfophthalein with mitochondrial membranes. Uptake of bromosulfophthalein and effect on ANS-fluorescence. Biochem Pharmacol 26:457–460
Feld GK, Loeb PM, Berk RN, Wheeler HO (1975) The choleretic effect of iodipamide. J Clin Invest 55:528–535
Felder E, Tanara CB (1976) Radiopaque contrast media. Farm Ed Prat 31:283–294
Frimmer M (1982) Organotropism by carrier mediated transport. Trends Pharmacol Sci 3:395–397
Frimmer M, Petzinger E, Ziegler K (1980) Protective effects of anionic cholecystographic agents against phalloidin on isolated hepatocytes by competitive inhibition of the phallotoxin uptake. Naunyn-Schmiedeberg's Arch Pharmacol 313:85–89
Goresky CA (1964) Initial distribution and rate of uptake of sulfobromophthalein in the liver. Am J Physiol 207:13–26
Klingenberg M, Pfaff E (1967) Means of terminating reactions. Meth Enzymol 10:680–684
Kristensen LO (1980) Energenization of alanine transport in isolated rat hepatocytes. J Biol Chem 255:5236–5243
Lamprecht W, Trautschold I (1970) Adenosin-5′-triphosphat: Bestimmung mit Hexokinase und Glucose-6-phosphat Dehydrogenase. In: Bergmeyer HU (ed) Methoden der enzymatischen Analyse. Verlag Chemie, Weinheim, pp 2024–2033
Laperche Y, Oudea P (1976) Inhibition by sulfobromophthalein of mitochondrial translocation of anions and adenine nucleotides: Effects upon liver adenosine triphosphate and possible correlation with inhibition of bile flow in the rat. J Pharmacol Exp Ther 197:235–244
Levi AJ, Gatmaitan T, Arias IM (1969) Two hepatic cytoplasmic protein fractions, Y and Z, and their possible role in the hepatic uptake of bilirubin, sulfobromophthalein and other anions. J Clin Invest 48:2156–2167
Loeb PM, Berk RN, Feld GK (1975) Biliary excretion of iodipamide. Gastroenterology 68:554–562
Lunazzi G, Tiribelli C, Gazzin B, Sottocasa G (1982) Further studies on bilitranslocase, a plasma membrane protein involved in hepatic organic anion uptake. Biochim Biophys Acta 685:117–123
Mäenpää PH, Raivio KO, Kekomäki MP (1968) Liver adenin nucleotides: Fructose-induced depletion and its effect on protein synthesis. Science 161:1253–1254
Minder E, Paumgartner G (1979) Dispartate Na+ requirement of taurocholate and indocyanine green uptake by isolated hepatocyte. Experientia 35:888–890
Müller WE, Stillbauer AE (1980) Liver slice uptake of intravenous and oral biliary contrast media. Arch Int Pharmacodyn Ther 246: 187–204
Paumgartner G, Reichen J (1975) Different pathways for hepatic uptake of taurocholate and indocyanine green. Experientia 31:306–308
Paumgartner G, Reichen J (1976) Kinetics of hepatic uptake of unconjugated bilirubin. Clin Sci Mol Med 54:169–176
Petzinger E, Frimmer M (1982) Energy linked uptake of demethylphalloin by isolated rat liver cells. Naunyn-Schmiedeberg's Arch Pharmacol 319:87–92
Petzinger E, Ziegler K, Frimmer M (1979) Inhibition of 3H-demethylphalloin uptake in isolated rat hepatocytes under various experimental conditions. Naunyn-Schmiedeberg's Arch Pharmacol 307:275–281
Piller M (1963) Eiweißbindung und Verteilung von Bromsulphalein im Organismus. Schweizer Med Wochenschr 93:1034–1039
Reichen J, Berk PD (1979) Isolation of an organic anion binding protein from rat liver plasma membrane fractions by affinity chromatography. Biochem Biophys Res Commun 91:484–489
Reichen J, Blitzer BL, Berk PD (1981) Binding of unconjugated and conjugated sulfobromophthalein to rat liver plasma membrane fractions in vitro. Biochim Biophys Acta 640:298–312
Schwarz LR, Burr R, Schwenk R, Pfaff E, Greim H (1975) Uptake of taurocholic acid into isolated rat liver cells. Eur J Biochem 55: 617–623
Schwenk M, Burr R, Schwarz L, Pfaff E (1976) Uptake of bromosulfophthalein by isolated liver cells. Eur J Biochem 64:189–197
Schwenk M, Burr R, Baur H, Pfaff E (1977) Interaction of bromosulfophthalein with mitochondrial membranes: Effect on ion movements. Biochem Pharmacol 26:825–832
Sokoloff J, Berk RN, Lang JH, Lasser EC (1973) The role of the Y and Z hepatic proteins in the excretion of radiographic contrast materials. Radiology 106:519–523
Sottocasa GL, Baldini G, Sandri G, Tiribelli C (1982) Reconstitution in vitro of sulfobromophthalein transport by bilitranslocase. Biochim Biophys Acta 685:117–123
Sperber I, Sperber G (1971) Hepatic excretion of radiocontrast agents. In: Knoefel PK (ed) Radiocontrast agents, vol 1. Pergamon Press, London, pp 165–235
Tiribelli C, Lunazzi G, Luciani M, Panfili E, Gazzin B, Lint G, Sandri G, Sottocasa G (1975) Isolation of a sulfobromophthalein-binding protein from hepatocytes plasma membrane. Biochim Biophys Acta 532:105–112
van Bezooijen CFA, Grell T, Knook DL (1976) Bromosulfophthalein uptake by isolated liver parenchymal cells. Biochem Biophys Res Commun 69:354–361
Vonk RJ, Jekel PA, Meijer DKF, Hardonk MJ (1978) Transport of drugs in isolated hepatocytes. The influence of bile salts. Biochem Pharmacol 27:397–405
Vonk RJ, Danhof M, Coenraads T, Van Dorn ABD, Keulemans K, Scaf AHJ, Meijer DKF (1979) Influence of bile salts on hepatic transport of dibromosulphthalein. Am J Physiol 237(6):E524-E534
Ziegler K, Petzinger E, Grundmann E, Frimmer M (1979) Decreased sensitivity of isolated hepatocytes from baby rats, from regenerating and from poisoned livers to phalloidin. Naunyn-Schmiedeberg's Arch Pharmacol 306:295–300
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This work was supported by the Deutsche Forschungsgemeinschaft
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Petzinger, E., Joppen, C. & Frimmer, M. Common properties of hepatocellular uptake of cholate, iodipamide and antamanide, as distinct from the uptake of bromosulfophthalein. Naunyn-Schmiedeberg's Arch. Pharmacol. 322, 174–179 (1983). https://doi.org/10.1007/BF00512393
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DOI: https://doi.org/10.1007/BF00512393