Interaction of hydroxycinnamic acids and their conjugates with organic anion transporters and ATP-binding cassette transporters

Chi C. Wong, Denis Barron, Caroline Orfila, Fabiola Dionisi, Peter Krajcsi, Gary Williamson

Research output: Contribution to journalArticleResearchpeer-review

23 Citations (Scopus)

Abstract

Scope: Hydroxycinnamic acids are abundant antioxidants in our diet. In humans, hydroxycinnamic acids are metabolized to form sulfates and glucuronides, with the majority recovered in urine. Methods and results: We assessed the potential roles of organic anion transporters (OATs) and ATP-binding cassette (ABC) transporters in the renal uptake and efflux of hydroxycinnamic acid conjugates. Uptake studies using OAT1 (SLC22A6)-, OAT2 (SLC22A7)-, and OAT3 (SLC22A8)-expressing 293H embryonic kidney cells showed that OAT1 and OAT3, but not OAT2, accepted hydroxycinnamic acid conjugates as substrates. OAT1 and OAT3 mediated the basolateral uptake of hydroxycinnamic acid sulfates and glucuronide conjugates, respectively. Hydroxycinnamic acid sulfates are substrates of OAT4 and were capable of trans-stimulating 5-carboxyfluorescein uptake mediated by OAT4. On the other hand, hydroxycinnamic acid conjugates are not substrates for the ABC transporters, multidrug resistance protein 2 (MRP2/ABCC2) or breast cancer resistance protein (BCRP/ABCG2), demonstrated by the inability to alter ATPase activity. Cis-inhibition studies with OATs and MRPs revealed that hydroxycinnamic acid conjugates have limited impact on the transport of model substrates significantly at physiological concentrations. Conclusion: Concerted action of OAT1, OAT3, and OAT4 is involved in the elimination of hydroxycinnamic acid conjugates into urine, whereas MRP2 and breast cancer resistance protein are not involved in the disposition of these conjugates.

Original languageEnglish
Pages (from-to)979-988
Number of pages10
JournalMolecular Nutrition & Food Research
Volume55
Issue number7
DOIs
Publication statusPublished - 1 Jul 2011
Externally publishedYes

Keywords

  • Bioavailability
  • Hydroxycinnamic acids
  • Multidrug resistance transporters
  • Organic anion transporters

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