Functional characterization of a human organic anion transporter hOAT4 in placental BeWo cells

Eur J Pharm Sci. 2006 Apr;27(5):518-23. doi: 10.1016/j.ejps.2005.09.008. Epub 2005 Oct 27.


Human organic anion transporter 4 (hOAT4) belongs to a family of organic anion transporters which play critical roles in the body disposition of clinically important drugs, including anti-HIV therapeutics, anti-tumor drugs, antibiotics, anti-hypertensives, and anti-inflammatories. hOAT4 is expressed in the placenta and kidney. In the current study, we stably transfected hOAT4 into human placental BeWo cells and the functional properties of hOAT4 and its regulation were investigated in these cells. hOAT4-mediated uptake of estrone sulfate, a protypical organic anion for hOAT4, was dose- and time-dependent, and saturable (Km=4.2 microM). The substrate specificity of hOAT4 includes various steroid sulfates, such as beta-estradiol-3,17-disulfate, 17-beta-estradiol-3-sulfate, beta-estradiol-3-sulfate, and dehydroepiandrosterone-3-sulfate (DHEAS), but does not include p-aminohippuric acid (PAH) and tetraethylammonium (TEA). Pre-incubation of hOAT4-expressing BeWo cells with phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-dibutyrate (PDBu), both of which are protein kinase C (PKC) activators, acutely inhibited the transport activity. The inhibition by PDBu resulted in a decreased Vmax without significant affecting the Km. Establishment of hOAT4-expressing BeWo cells provided useful tool for further pharmacological and molecular biological studies of placental transport of organic anions mediated by this carrier.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line
  • Dehydroepiandrosterone Sulfate / metabolism
  • Enzyme Activation / drug effects
  • Estradiol / analogs & derivatives
  • Estradiol / metabolism
  • Estrone / analogs & derivatives
  • Estrone / metabolism
  • Humans
  • Kinetics
  • Organic Anion Transporters, Sodium-Independent / antagonists & inhibitors
  • Organic Anion Transporters, Sodium-Independent / genetics
  • Organic Anion Transporters, Sodium-Independent / metabolism*
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Placenta / drug effects
  • Placenta / enzymology
  • Placenta / metabolism*
  • Protein Kinase C / metabolism*
  • Tetradecanoylphorbol Acetate / analogs & derivatives
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transfection


  • Organic Anion Transporters, Sodium-Independent
  • SLC22A11 protein, human
  • Estrone
  • estradiol 3,17-disulfate
  • Phorbol 12,13-Dibutyrate
  • Estradiol
  • phorbolol myristate acetate
  • Dehydroepiandrosterone Sulfate
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate
  • estrone sulfate