FUNCTIONAL INVOLVEMENT OF RAT ORGANIC ANION TRANSPORTER 2 (SLC22A7) IN THE HEPATIC UPTAKE OF THE NONSTEROIDAL ANTI-INFLAMMATORY DRUG KETOPROFEN

2005 ◽  
Vol 33 (8) ◽  
pp. 1151-1157 ◽  
Author(s):  
Naomi Morita ◽  
Hiroyuki Kusuhara ◽  
Yoshitane Nozaki ◽  
Hitoshi Endou ◽  
Yuichi Sugiyama
Keyword(s):  
Organic Anion ◽  
Hepatic Uptake ◽  
Organic Anion Transporter ◽  
Inflammatory Drug ◽  
Anion Transporter ◽  
Functional Involvement ◽  
Anti Inflammatory

scholarly journals Hepatic Uptake of Bilirubin and Its Conjugates by the Human Organic Anion Transporter SLC21A6

2000 ◽  
Vol 276 (13) ◽  
pp. 9626-9630 ◽  
Author(s):  
Yunhai Cui ◽  
Jörg König ◽  
Inka Leier ◽  
Ulrike Buchholz ◽  
Dietrich Keppler
Keyword(s):  
Organic Anion ◽  
Hepatic Uptake ◽  
Organic Anion Transporter ◽  
Anion Transporter

scholarly journals Evaluation of the endothelin receptor antagonists ambrisentan, darusentan, bosentan, and sitaxsentan as substrates and inhibitors of hepatobiliary transporters in sandwich-cultured human hepatocytesThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.

2010 ◽  
Vol 88 (6) ◽  
pp. 682-691 ◽  
Author(s):  
J. Craig Hartman ◽  
Kenneth Brouwer ◽  
Arun Mandagere ◽  
Lawrence Melvin ◽  
Richard Gorczynski
Keyword(s):  
Organic Anion ◽  
Hepatic Uptake ◽  
Organic Anion Transporter ◽  
Endothelin Receptor Antagonists ◽  
Endothelin Receptor ◽  
Transport Activity ◽  
Receptor Antagonists ◽  
P Glycoprotein ◽  
Anion Transporter ◽  
Hepatic Transporters

To evaluate potential mechanisms of clinical hepatotoxicity, 4 endothelin receptor antagonists (ERAs) were examined for substrate activity and inhibition of hepatic uptake and efflux transporters in sandwich-cultured human hepatocytes. The 4 transporters studied were sodium-dependent taurocholate cotransporter (NTCP), organic anion transporter (OATP), bile salt export pump (BSEP), and multidrug resistance-associated protein 2 (MRP2). ERA transporter inhibition was examined using the substrates taurocholate (for NTCP and BSEP), [3H]estradiol-17β-d-glucuronide (for OATP), and [2-d-penicillamine, 5-d-penicillamine]enkephalin (for MRP2). ERA substrate activity was evaluated using probe inhibitors ritonavir (OATP and BSEP), bromosulfalein (OATP), erythromycin (P-glycoprotein), probenecid (MRP2 and OATP), and cyclosporin (NTCP). ERAs were tested at 2, 20, and 100 µmol·L–1 for inhibition and at 2 µmol·L–1 as substrates. OATP, NTCP, or BSEP transport activity was not reduced by ambrisentan or darusentan. Bosentan and sitaxsentan attenuated NTCP transport at higher concentrations. Only sitaxsentan decreased OATP transport (52%), and only bosentan reduced BSEP transport (78%). MRP2 transport activity was unaltered. OATP inhibitors decreased influx of all ERAs. Darusentan influx was least affected (84%–100% of control), whereas bosentan was most affected (32%–58% of control). NTCP did not contribute to influx of ERAs. Only bosentan and darusentan were shown as substrates for both BSEP and P-glycoprotein efflux. All ERAs tested were substrates for at least one hepatic transporter. Bosentan and sitaxsentan, but not ambrisentan and darusentan, inhibited human hepatic transporters, which provides a potential mechanism for the increased hepatotoxicity observed for these agents in the clinical setting.

scholarly journals Effect of Organic Anion Transporters on the Development of Nephrotoxicity in the Context of NSAIDs Use

2020 ◽  
Vol 8 (4) ◽  
pp. 198-204
Author(s):  
O. V. Muslimova ◽  
V. A. Evteev ◽  
I. A. Mazerkina
Keyword(s):  
Adverse Reactions ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Renal Diseases ◽  
Tubular Necrosis ◽  
Anion Transporters ◽  
Anion Transporter ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used worldwide as pain relievers, antipyretics, and anti-inflammatory drugs. Failure to comply with the instructions for medical use of this group of drugs increases the risk of serious adverse reactions on the part of different organs and systems. From 5 to 18% of patients taking NSAIDs develop adverse reactions associated with impaired renal function. Organic anion transporter (OAT) proteins, which mediate the drug excretion with urine, have an important role to play in the NSAIDs adverse effect on kidneys. The aim of the study was to analyse and systematize scientific literature on the role of OATs in nephrotoxicity development in the context of NSAIDs use. It was revealed that adverse kidney reactions associated with NSAIDs are determined by several mechanisms, including inhibition of prostaglandin synthesis due to cyclooxeganse-1 and/or cyclooxeganse-2 blockade, and direct toxic effect on renal tubule epithelium followed by tubular necrosis due to NSAIDs interaction with OATs. Moreover, by suppressing OAT1 and OAT3, NSAIDs can not only enhance, but also reduce nephrotoxic effects of other medicines (when used together) and endogenous/exogenous toxins. Considering that NSAIDs are widely used in the treatment of various diseases (including in elderly patients and patients with concomitant renal diseases), it is still relevant to study mechanisms of adverse kidney reactions associated with drug transporters.

scholarly journals Organic Anion Transporter 2 Mediates Hepatic Uptake of Tolbutamide, a CYP2C9 Probe Drug

2018 ◽  
Vol 364 (3) ◽  
pp. 390-398 ◽  
Author(s):  
Yi-an Bi ◽  
Sumathy Mathialagan ◽  
Laurie Tylaska ◽  
Myra Fu ◽  
Julie Keefer ◽  
...  
Keyword(s):  
Organic Anion ◽  
Hepatic Uptake ◽  
Organic Anion Transporter ◽  
Probe Drug ◽  
Anion Transporter
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