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ATP-dependent 17-beta-estradiol 17- transport by multidrug resistance protein Inhibition by cholestatic steroids


, : ATP-dependent 17-beta-estradiol 17- transport by multidrug resistance protein Inhibition by cholestatic steroids. Journal of Biological Chemistry 271(16): 9683-9689

In addition to its ability to confer resistance to a range of natural product type chemotherapeutic agents, multidrug resistance protein (MRP) has been shown to transport the cysteinyl leukotriene, LTC-4, and several other glutathione (GSH) S-conjugates. We now demonstrate that its range of potential physiological substrates also includes cholestatic glucuronidated steroids. ATP dependent, osmotically sensitive transport of the naturally occurring conjugated estrogen, 17-beta-estradiol 17-(beta-D-glucuronide) (E-217-beta-G), was readily demonstrable in plasma membrane vesicles from populations of MRP-transfected HeLa cells (V-max 1.4 nmol mg-1 min-1, K-m 2.5 mu-M). The involvement of MRP was confirmed by demonstrating that transport was completely inhibited by a monoclonal antibody specific for an intracellular conformational epitope of the protein. MRP-mediated transport of LTC-4 was competitively inhibited by E-217-beta-G (K-i(app) 22 mu-M), despite the lack of structural similarity between these two substrates. Competitive inhibition of (3H)E-217-beta-G transport was also observed with a number of other cholestatic conjugated steroids. All of these compounds prevented photolabeling of MRP with (3H)LTC-4, demonstrating that the cholestatic steroid and leukotriene conjugates compete either for the same or possibly overlapping sites on the protein. Consistent with the presence of overlapping but non-identical sites, studies using chemotherapeutic drugs to inhibit MRP-mediated E-217-beta-G transport indicated that daunorubicin had the highest relative potency of the drugs tested, whereas it was the least potent inhibitor of LTC-4 transport. Non-cholestatic steroids glucuronidated at the 3 position of the steroid nucleus, such as 17-beta-estradiol 3-(beta-D-glucuronide), did not compete for transport of E-217-beta-G by MRP, nor did they inhibit photolabeling of the protein with (3H)LTC-4. These data identify MRP as a potential transporter of cholestatic conjugated estrogens and demonstrate site-specific requirements for glucuronidation of the steroid nucleus.

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Other references

Simmen, H.P.; Lüthy, R.; Siegenthaler, W., 1981: Use of antibiotics in ambulatory care. Results and reflections on a survey of practicing physicians in the canton of Zurich. To survey antibiotic use in general practice, questionnaires were sent to 1160 practitioners in the Canton of Zurich. 510 (44%) were returned. Antibiotics had been administered for respiratory tract infections in 60% and urinary tract infections i...

Wapner, Seymour, 1944: The differential effects of cortical injury and retesting on equivalence reactions in the rat. The effects of cortical injury and retesting (experience) on equivalence behavior were studied. After a careful description of the equivalence method and its application in this expt., the author finds that operating and retesting had differential...

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Dyer, H.M.; Roe, J.H., 1934: The chemistry of the blood of normal chickens. Values for 23 constituents of the blood of normal hens are given. The method of analysis used, the number of hens examined, the number of detns., the lowest and the highest individual values, and the av. value for each constituent are reported.

Borneuf, Dm, 1983: Automatic soil suction measurements. Verslagen en mededelingen Commissie voor Hydrologisch Onderzoek TNO: (31) 502-512

Lamontagne, Y., 1991: Medical marketing in the media. The mass-media monopolize an important part of the lay public attention and intellectual energy and yet physicians do not seem very convinced that they must implicate themselves socially and participate in the education of the general public. Two...

Chen W G.; Hwang G.C C., 1992: Adhesive and in vitro release characteristics of propranolol bioadhesive disc system. For the study of bioadhesive systems used in the controlled delivery of drugs-through the oral mucosal membrane, direct compressed disc systems containing either 10, 15 or 20 mg of propranolol HCl (PL) with a mixture of hydroxypropyl cellulose and...

Islebe Gerald, 1996: The late glacial-Holocene transition in mountainous Costa Rica. Terra Nostra (Bonn) 8-96: 68

D.L.Pena, A., 1960: Charles V and 2 humanistic physicians (Andres Laguna, Francisco Valles). Urologia Internationalis 10: 5-18

Chen, Q.; Veenman, L.; Knopp, K.; Yan, Z.; Medina, L.; Song, W.J.; Surmeier, D.J.; Reiner, A., 1998: Evidence for the preferential localization of glutamate receptor-1 subunits of AMPA receptors to the dendritic spines of medium spiny neurons in rat striatum. Although immunohistochemical studies have typically found the perikarya of striatal projection neurons to be devoid of immunohistochemical labelling for the GluR1 AMPA type glutamate receptor subunit, the striatal neuropil is rich in GluR1 immunol...