title: Ribosomal protein L3 mediated the transport of digoxin in Xenopus laevis oocyte.
abstract: Ribosomal protein L3 (RPL3) is known to be an indispensable and essential component for the peptidyltransferase center. In the present study, we found a novel function of RPL3 using a Xenopus laevis oocyte expression system. When expressed in X. oocytes, RPL3 mediated the high affinity transport of [(3)H]digoxin (K(m) = 213.3 ± 46.8 nM) in a time-, concentration-, and sodium-dependent manners. The maximum velocity of the transport of [(3)H]digoxin via RPL3 produced at physiological pH. However, we did not observe RPL3-mediated transport of several organic solutes such as [(14)C]androstenedione, [(3)H]dexamethasone, [(3)H]dehydroepiandrosterone sulfate, [(3)H]L-tryptophan, [(14)C]L-ascorbic acid, [(14)C]α-ketoglutarate, [(14)C]glutarate, [(3)H]methotrexate, [(3)H]bumetanide, [(3)H]probenecid, [(14)C]salicylic acid, [(14)C]theophylline and [(3)H]valproate. Our results suggest that RPL3 functions as a drug carrier protein and may be involved in the digoxin toxicity in the human body.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Showa University, Tokyo, Japan.
authors.forename: Yasuna
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Kanako
authors.initials: K
authors.lastname: Kawakami
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohbayashi
authors.forename: Noriko
authors.initials: N
authors.lastname: Kohyama
authors.forename: Toshinori
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000096:biosynthesis / Q000502:physiology*; D018076:DNA, Complementary / Q000096:biosynthesis; D004077:Digoxin / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009865:Oocytes / Q000378:metabolism*; D018075:RNA, Complementary / Q000096:biosynthesis; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins / Q000096:biosynthesis / Q000502:physiology*; D014316:Tritium; D014982:Xenopus laevis
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D018075:RNA, Complementary; C000716547:RPL3 protein, human; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins; D014316:Tritium; D004077:Digoxin