Characterization of an Organic Anion-Transporting Polypeptide (OATP-B) in Human Placenta

Abstract

Organic anion-transporting polypeptides (OATPs) are a family of multispecific carriers that mediate the sodium-independent transport of steroid hormone and conjugates, drugs, and numerous anionic endogenous substrates. We investigated whether members of the OATP gene family could mediate fetal-maternal transfer of anionic steroid conjugates in the human placenta. OATP-B (gene symbol SLC21A9) was isolated from a placenta cDNA library. An antiserum to OATP-B detected an 85-kDa protein in basal but not apical syncytiotrophoblast membranes. Immunohistochemistry of first-, second-, and third-trimester placenta showed staining in the cytotrophoblast membranes and at the basal surface of the syncytiotrophoblast. Trophoblasts that reacted with an antibody to Ki-67, a proliferation-associated antigen, expressed lower levels of OATP-B. OATP-B mRNA levels were measured in isolated trophoblasts under culture conditions that promoted syncytia formation. Real-time quantitative PCR estimated an 8-fold increase in OATP-B expression on differentiation to syncytia. The uptake of [ 3 H]estrone-3-sulfate, a substrate for OATP-B, was measured in basal syncytiotrophoblast membrane vesicles. Transport was saturable and partially inhibited by pregnenolone sulfate, a progesterone precursor. Pregnenolone sulfate also partially inhibited OATP-B-mediated transport of estrone-3-sulfate in an oocyte expression system. These findings suggest a physiological role for OATP-B in the placental uptake of fetal-derived sulfated

Evaluation of Proposed In Vivo Probe Substrates and Inhibitors for Phenotyping Transporter Activity in Humans

“…OATP1B1 is expressed uniformly, whereas OATP1B3 is expressed more in the perivenous section. OATP2B1 is expressed on the basal side of hepatocytes and the apical membrane of intestinal enterocytes, as well as in the heart, brain, and placenta . OATP1A2 is present on vascular endothelial cells in the brain and transports substances across the blood–brain barrier .…”

Mother-to-fetus transfer of antiviral drugs and the involvement of transporters at the placental barrier

“…The fetal‐facing basolateral membrane of the syncytiotrophoblast expresses organic anion transporter 4 (OAT4/SLC22A11),43 organic cation transporter 3 (OCT3/SLC22A3),45 and organic anion transporting polypeptide 2B1 (OATP2B1/SLCO2B1) 49. Although it is impossible to clarify the role of OAT4 by using gene‐knockout mice because OAT4 is specific to humans and primates, it has been established that tetracyline, methotrexate, bumetanide, ketoprofen, and salicylate are substrates for human OAT4 50.…”

Enzyme‐ and transporter‐mediated beverage–drug interactions: An update on fruit juices and green tea

“…The expression of OATP1B1 and OATP1B3 is confined to the liver, and these 2 transporters have been reported to play an important role in hepatic uptake of xenobiotics across the sinusoidal membrane from blood . In contrast to the tissue‐specific expression of OATP1B1 and OATP1B3, OATP2B1 is localized in several tissues, including liver, small intestine, spleen, and placenta . OATP2B1 is expressed in significant amounts on the apical membrane of small intestinal epithelial cells, thereby facilitating the transfer of its substrates from the intestine to the bloodstream.…”