Characterization of two splice variants of human organic anion transporting polypeptide 3A1 isolated from human brain

Huber, R.; Gao, Bo; Pfändler, Marguerite-Anne Sidler; Zhang-Fu, Wenting; Leuthold, Simone; Hagenbuch, Bruno; Folkers, Gerd; Meier, Peter J.; Stieger, Bruno

doi:10.1152/ajpcell.00597.2005

Cited by 146 publications

(138 citation statements)

References 38 publications

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“…CSC was finally prepared by dissolving the collected smoke particulates in dimethyl sulfoxide were from Enzo Life Sciences (Villeurbanne, France), whereas mouse monoclonal antibody against heat shock cognate protein (HSC) 70 (clone B-6) was from Santa Cruz Biotechnology (Dallas, TX). Mouse monoclonal antibody against aryl hydrocarbon receptor (AhR) (clone RPT1) was supplied by Abcam (Cambridge, United Kingdom), whereas rabbit polyclonal antibody raised against OATP2B1 has been previously described (Huber et al 2007). All other chemicals and reagents were commercial products of the highest purity available.…”

Section: Chemicals and Reagentsmentioning

confidence: 99%

Alteration of human hepatic drug transporter activity and expression by cigarette smoke condensate

et al. 2016

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Smoking is well-known to impair pharmacokinetics, through inducing expression of drug metabolizing enzymes. In the present study, we demonstrated that cigarette smoke condensate (CSC) also alters activity and expression of hepatic drug transporters, which are now recognized as major actors of hepatobiliary elimination of drugs. CSC thus directly inhibited activities of sinusoidal transporters such as OATP1B1, OATP1B3, OCT1 and NTCP as well as those of canalicular transporters like P-glycoprotein, MRP2, BCRP and MATE1, in hepatic transporters-overexpressing cells. CSC similarly counteracted constitutive OATP, NTCP and OCT1 activities in human highly-differentiated hepatic HepaRG cells. In parallel, CSC induced expression of BCRP at both mRNA and protein level in HepaRG cells, whereas it concomitantly repressed mRNA expression of various transporters, including OATP1B1, OATP2B1, OAT2, NTCP, OCT1 and BSEP, and enhanced that of MRP4. Such changes in transporter gene expression were found to be highly correlated to those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin, a reference activator of the aryl hydrocarbon receptor (AhR) pathway, and were counteracted, for some of them, by siRNA-mediated AhR silencing. This suggests that CSC alters hepatic drug transporter levels via activation of the AhR cascade. Importantly, drug transporter expression regulations as well as some transporter activity inhibitions occurred for a range of CSC concentrations similar to those required for inducing drug metabolizing enzymes and may therefore be hypothesized to be relevant for smokers. Taken together, these data established human hepatic transporters as targets of cigarette smoke, which could contribute to known alteration of pharmacokinetics and some liver adverse effects caused by smoking. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. SummarySmoking is well-known to impair pharmacokinetics, through inducing expression of drug metabolizing enzymes. In the present study, we demonstrated that cigarette smoke condensate (CSC) also alters activity and expression of hepatic drug transporters, which are now recognized as major actors of hepatobiliary elimination of drugs. CSC thus directly inhibited activities of sinusoidal transporters such as OATP1B1, OATP1B3, OCT1 and NTCP as well as those of canalicular transporters like P-glycoprotein, MRP2, BCRP and MATE1, in hepatic transporters-overexpressing cells. CSC similarly counteracted constitutive OATP, NTCP and OCT1 activities in human highly-differentiated hepatic HepaRG cells. In parallel, CSC induced expression of BCRP at both mRNA and protein level in HepaRG ce...

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Section: Chemicals and Reagentsmentioning

confidence: 99%

Alteration of human hepatic drug transporter activity and expression by cigarette smoke condensate

et al. 2016

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“…Estrone-3-sulfate [35] p-Aminohippuric acid [170] Benzylpenicillin [35] Prostaglandin E1 [170,171] 0.05 Prostaglandin D2 [170] Prostaglandin E2 [35,170,171] 0.06 Prostaglandin E1 [170] Prostaglandin F2a [170] Prostaglandin E2 [170] Thyroxine [171] Prostaglandin F2a [170] Vasopressin [171] OATP4A1 (OATP-E) E217bG [35] Benzylpenicillin [35] Estrone-3-sulfate [35] Prostaglandin E2 [35] Reverse triiodothyronine [38] Taurocholate [38] 15 Thyroxine [38] Triiodothyronine [38] 0.9 OSTa/b DHEAS [39] Estrone-3-sulfate [172] Digoxin [172] Digoxin [172] Estrone-3-sulfate [39,172] 320 Glycolithocholic acid [172] Indometacin [172] Glycochenodeoxycholate [39] Glycolithocholic acid sulfate [172] Probenecid [172] Glycocholate [39] Lithocholic acid sulfate [172] Spironolactone [172] Glycodeoxycholate [39] Taurolithocholate [172] Glycoursodeoxycholate [39] Taurolithocholicate sulfate [172] Prostaglandin E2 [172] Taurochenodeoxycholate [39] Taurocholate …”

Section: Oatp1a2 (Oatp-a)mentioning

confidence: 99%

Intestinal transporters for endogenic and pharmaceutical organic anions: the challenges of deriving in-vitro kinetic parameters for the prediction of clinically relevant drug–drug interactions

Grandvuinet

Vestergaard

Rapin³

et al. 2012

Journal of Pharmacy and Pharmacology

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Objectives This review provides an overview of intestinal human transporters for organic anions and stresses the need for standardization of the various in‐vitro methods presently employed in drug–drug interaction (DDI) investigations. Key findings Current knowledge on the intestinal expression of the apical sodium‐dependent bile acid transporter (ASBT), the breast cancer resistance protein (BCRP), the monocarboxylate transporters (MCT) 1, MCT3‐5, the multidrug resistance associated proteins (MRP) 1–6, the organic anion transporting polypetides (OATP) 2B1, 1A2, 3A1 and 4A1, and the organic solute transporter α/β (OSTα/β) has been covered along with an overview of their substrates and inhibitors. Furthermore, the many challenges in predicting clinically relevant DDIs from in‐vitro studies have been discussed with focus on intestinal transporters and the various methods for deducting in‐vitro parameters for transporters (Km/Ki/IC50, efflux ratio). The applicability of using a cut‐off value (estimated based on the intestinal drug concentration divided by the Ki or IC50) has also been considered. Summary A re‐evaluation of the current approaches for the prediction of DDIs is necessary when considering the involvement of other transporters than P‐glycoprotein. Moreover, the interplay between various processes that a drug is subject to in‐vivo such as translocation by several transporters and dissolution should be considered.

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“…Protein samples (30 µg) were denatured (1 hr, room temperature) in loading buffer (Laemmli sample buffer with dithiothreitol at 54mg/ml), separated by electrophoresis in 10% SDS-PAGE gels and blotted on nitrocellulose membranes. Blots were then probed 190 with primary antibody: rabbit polyclonal antisera to MCT8 (Ab4790), MCT10 (described in [34]), OATP1A2 or OATP4A1 (described in [35]) or anti-human CD98 goat polyclonal 9 antibody (Santa Cruz). Primary antibodies were used at 1:500, with the exception of the anti-CD98 (1:250).…”

Section: Western Blotmentioning

confidence: 99%

Expression of thyroid hormone transporters in the human placenta and changes associated with intrauterine growth restriction

et al. 2010

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Characterization of two splice variants of human organic anion transporting polypeptide 3A1 isolated from human brain

Cited by 146 publications

References 38 publications

Alteration of human hepatic drug transporter activity and expression by cigarette smoke condensate

Alteration of human hepatic drug transporter activity and expression by cigarette smoke condensate

Intestinal transporters for endogenic and pharmaceutical organic anions: the challenges of deriving in-vitro kinetic parameters for the prediction of clinically relevant drug–drug interactions

Expression of thyroid hormone transporters in the human placenta and changes associated with intrauterine growth restriction

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