Role of Uptake Transporters OAT4, OATP2A1, and OATP1A2 in Human Placental Bio-disposition of Pravastatin

Fokina, Valentina M.; Patrikeeva, Svetlana; Wang, Xiao ming; Noguchi, Saki; Tomi, Masatoshi; König, Jörg; Ahmed, Mahmoud S.; Nanovskaya, Tatiana

doi:10.1016/j.xphs.2021.09.035

Cited by 5 publications

(7 citation statements)

References 51 publications

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“…Although drug transporters facilitate the passage of both endogenous and exogenous substrates across cellular membranes, in this review, we focus on the role of drug [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]. ATP-binding cassette (ABC) transporters are depicted in blue, solute carrier (SLC) transporters in green, and an immunoglobulin transporter in orange.…”

Section: Drug Transportersmentioning

confidence: 99%

“…Observed in the liver, kidney, intestine, central nervous system, skeletal muscle, heart, lung, pancreas, and adrenal gland, OATs are anion exchangers that pair the uptake of an anionic substrate with the efflux of another anion [44]. Though OAT1-3 are predominantly expressed in excretory organs [16], OAT4 mediates the transport of anions [27] and the uptake of estrogen precursors [46] in the placenta.…”

Section: Organic Anion Transporter (Oat) Familymentioning

confidence: 99%

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A Literature Review of Changes in Phase II Drug-Metabolizing Enzyme and Drug Transporter Expression during Pregnancy

Gong,

Bertagnolli,

Boulton

et al. 2023

Pharmaceutics

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The purpose of this literature review is to comprehensively summarize changes in the expression of phase II drug-metabolizing enzymes and drug transporters in both the pregnant woman and the placenta. Using PubMed®, a systematic search was conducted to identify literature relevant to drug metabolism and transport in pregnancy. PubMed was searched with pre-specified terms during the period of 26 May 2023 to 10 July 2023. The final dataset of 142 manuscripts was evaluated for evidence regarding the effect of gestational age and hormonal regulation on the expression of phase II enzymes (n = 16) and drug transporters (n = 38) in the pregnant woman and in the placenta. This comprehensive review exposes gaps in current knowledge of phase II enzyme and drug transporter localization, expression, and regulation during pregnancy, which emphasizes the need for further research. Moreover, the information collected in this review regarding phase II drug-metabolizing enzyme and drug transporter changes will aid in optimizing pregnancy physiologically based pharmacokinetic (PBPK) models to inform dose selection in the pregnant population.

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Section: Drug Transportersmentioning

confidence: 99%

Section: Organic Anion Transporter (Oat) Familymentioning

confidence: 99%

A Literature Review of Changes in Phase II Drug-Metabolizing Enzyme and Drug Transporter Expression during Pregnancy

Gong,

Bertagnolli,

Boulton

et al. 2023

Pharmaceutics

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“…In this process, SOAT is involved in the uptake of DHEAS via the maternal-facing microvillous plasma membrane of the syncytiotrophoblast and in the transport across the fetal blood vessel endothelium. In addition, the carriers OATP2B1 and OAT4 are involved in the transport of DHEAS and 16α-DHEAS across the basal plasma membrane of the syncytiotrophoblast, which is oriented toward the fetal circulation [ 49 , 88 , 89 , 90 , 91 ]. Low estriol concentrations during pregnancy have been correlated with fetal disorders such as Down syndrome or anencephaly [ 92 , 93 ].…”

Section: Role Of Soat In Health and Diseasementioning

confidence: 99%

Role of the Sodium-Dependent Organic Anion Transporter (SOAT/SLC10A6) in Physiology and Pathophysiology

Wannowius

Karakuş

Aktürk

et al. 2023

IJMS

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The sodium-dependent organic anion transporter (SOAT, gene symbol SLC10A6) specifically transports 3′- and 17′-monosulfated steroid hormones, such as estrone sulfate and dehydroepiandrosterone sulfate, into specific target cells. These biologically inactive sulfo-conjugated steroids occur in high concentrations in the blood circulation and serve as precursors for the intracrine formation of active estrogens and androgens that contribute to the overall regulation of steroids in many peripheral tissues. Although SOAT expression has been detected in several hormone-responsive peripheral tissues, its quantitative contribution to steroid sulfate uptake in different organs is still not completely clear. Given this fact, the present review provides a comprehensive overview of the current knowledge about the SOAT by summarizing all experimental findings obtained since its first cloning in 2004 and by processing SOAT/SLC10A6-related data from genome-wide protein and mRNA expression databases. In conclusion, despite a significantly increased understanding of the function and physiological significance of the SOAT over the past 20 years, further studies are needed to finally establish it as a potential drug target for endocrine-based therapy of steroid-responsive diseases such as hormone-dependent breast cancer.

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“…Other transporters, including MRPs 1–5, OATP1B1, OATP1B3, OCTN1, OCTN2, and the multidrug and toxin extrusion 1 (MATE1), can be detected in human placenta at the mRNA levels, but their protein abundance is below the quantifiable levels (see Figure 1 ) [ 45 ]. OATP2A1 protein was recently detected on the apical membrane of human placenta by immunoblotting [ 46 ]. Since the function or activity of these transporters in human placenta generally has not been well characterized, these transporters are not further discussed here.…”

Section: Expression Localization and Activity Of Major Placental Drug...mentioning

confidence: 99%

“…Whether this organoid model has the same or similar transporter expression profiles as in vivo and can be used to study placental drug transport remains to be investigated. Besides cell models, plasma membrane vesicles can be isolated from the microvillus (apical) and basal plasma membrane fractions of human placental villous tissues [ 56 ] and are of high value for direct measurement of transport kinetics of hydrophilic drugs into the vesicles by placental transporters [ 46 , 57 ].…”

Section: In Vitro Ex Vivo and In Vivo Sys...mentioning

confidence: 99%

An update on placental drug transport and its relevance to fetal drug exposure

Mao

Chen

2022

Medical Review

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Pregnant women are often complicated with diseases that require treatment with medication. Most drugs administered to pregnant women are off-label without the necessary dose, efficacy, and safety information. Knowledge concerning drug transfer across the placental barrier is essential for understanding fetal drug exposure and hence drug safety and efficacy to the fetus. Transporters expressed in the placenta, including adenosine triphosphate (ATP)-binding cassette efflux transporters and solute carrier uptake transporters, play important roles in determining drug transfer across the placental barrier, leading to fetal exposure to the drugs. In this review, we provide an update on placental drug transport, including in vitro cell/tissue, ex vivo human placenta perfusion, and in vivo animal studies that can be used to determine the expression and function of drug transporters in the placenta as well as placental drug transfer and fetal drug exposure. We also describe how the knowledge of placental drug transfer through passive diffusion or active transport can be combined with physiologically based pharmacokinetic modeling and simulation to predict systemic fetal drug exposure. Finally, we highlight knowledge gaps in studying placental drug transport and predicting fetal drug exposure and discuss future research directions to fill these gaps.

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Role of Uptake Transporters OAT4, OATP2A1, and OATP1A2 in Human Placental Bio-disposition of Pravastatin

Cited by 5 publications

References 51 publications

A Literature Review of Changes in Phase II Drug-Metabolizing Enzyme and Drug Transporter Expression during Pregnancy

A Literature Review of Changes in Phase II Drug-Metabolizing Enzyme and Drug Transporter Expression during Pregnancy

Role of the Sodium-Dependent Organic Anion Transporter (SOAT/SLC10A6) in Physiology and Pathophysiology

An update on placental drug transport and its relevance to fetal drug exposure

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