Abstract
The hypothesis that P-glycoprotein (P-gp) mediates the renal secretion of organic cations was tested by functional expression of mRNAs in theXenopus laevis oocyte system. Efflux of 2′-deoxytubercidin (dTub), a substrate for the renal organic cation transporter (OCT) but not for P-gp, was enhanced by injection of renal mRNA but not by injection of mRNA from P-gp-overexpressing cells (MDCK cells transduced with the cDNA for humanMDR1). The functional capacity of the MDCK-MDR mRNA was established by its ability to reduce, the steady-state uptake of a classical P-gp substrate, vinblastine. Thus, these data indicate OCT and P-gp to be distinct entities. TheXenopus oocyte system provides a functional approach to further characterize the OCT.
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Nelson JA (1988) A physiological function for multidrug-resistant membrane glycoproteins: a hypothesis regarding the renal organic cation-secretory system. Cancer Chemother Pharmacol 22:92
Thiebaut F, Tsuruo T, Hamada H, Gottesman MM, Pastan I, Willingham MC (1987) Cellular localization of the multidrugresistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci USA 84:7735
Kinsella J L, Holohan PD, Pessah NI, Ross CR (1979) Transport of organic ions in renal cortical luminal and antiluminal membrane vesicles. J Pharmacol Exp Ther 209:443
Dutt A, Priebe T S, Teeter L D, Kuo MT, Nelson JA (1992) Postnatal development of organic cation transport andMDR gene expression in mouse kidney. J Pharmacol Exp Ther 261:1222
Dutt A, Heath LA, Nelson JA (1994) P-glycoprotein and organic cation secretion by the mammalian kidney. J Pharmacol Exp Ther 269:1254
Holohan PD, Ross CR (1980) Mechanisms of organic cation transport in kidney plasma membrane vesicles: I. Countertransport studies. J Pharmacol Exp Ther 215:191
Holohan PD, Ross CR (1981) Mechanisms of organic cation transport in kidney plasma membrane vesicles: II. Δ pH studies. J Pharmacol Exp Ther 216:294
Horio M, Chin K-V, Currier SJ, Goldenberg S, Williams C, Pastan I, Gottesman MM, Handler J (1989) Transepithelial transport of drugs by the multidrug transporter in cultured Madin-Darby canine kidney cell epithelia. J Biol Chem 264:14880
Pan BF, Dutt A, Nelson JA (1994) Enhanced transepithelial flux of cimetidine by Madin-Darby canine kidney cells overexpressing human P-glycoprotein. J Pharmacol Exp Ther 270:1
Pan BF, Nelson JA (1994) P-glycoprotein and the renal secretion of deoxyribonucleosides. Nucleosides Nucleotides 13:1179
Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter W (1979) Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18:5294
Pajor AM, Wright EM (1992) Cloning and functional expression of a mammalian Na+/nucleoside cotrasporter. J Biol Chem 267:35557
Huang QQ, Harvey CM, Paterson ARP, Cass CE, Young JD (1993) Functional expression of Na+-dependent nucleoside transport systems of rat intestine in isolated oocytes ofXenopus laevis. J Biol Chem 268:20613
Huang QQ, Yao SYM, Ritzel MWL, Paterson ARP, Cass CE, Young JD (1994) Cloning and functional expression of a complementary DNA encoding a mammalian nucleoside transport protein. J Biol Chem 269:17757
Castillo G, Vera JC, Yang C-PH, Horwitz SB, Rosen OM (1990) Functional expression of murine multidrug resistance inXenopus laevis oocytes. Proc Natl Acad Sci (USA) 87:4737
Kuttesch J F jr, Nelson J A (1982) Renal handling of 2′-deoxyadenosine and adenosine in humans and mice. Cancer Chemother Pharmacol 8:221
Kuttesch JF Jr, Robins MJ, Nelson J A (1982) Renal transport of 2′-deoxytubercidin in mice. Biochem Pharmacol 31:3387
Nelson JA, Kuttesch JF jr, Herbert BH (1983) Renal secretion of purine nucleosides and their analogs in mice. Biochem Pharmacol 32:2323
DeLannoy IAM, Mandin RS, Silverman M (1994) Renal secretion of vinblastine, vincristine and colchicinein vivo. J Pharmacol Exp Ther 268:388
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Work supported by NIH Grant RO1DK41606 from the Institute for Digestive Diseases and Kidney, and NIH Cancer Center Core Grant, CA 16672 from the National Cancer Institute
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Nelson, J.A., Dutt, A., Allen, L.H. et al. Functional expression of the renal organic cation transporter and P-glycoprotein inXenopus laevis oocytes. Cancer Chemother. Pharmacol. 37, 187–189 (1995). https://doi.org/10.1007/BF00685648
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DOI: https://doi.org/10.1007/BF00685648