Preclinical and Clinical Evidence for the Collaborative Transport and Renal Secretion of an Oxazolidinone Antibiotic by Organic Anion Transporter 3 (OAT3/SLC22A8) and Multidrug and Toxin Extrusion Protein 1 (MATE1/SLC47A1)

2010 ◽  
Vol 334 (3) ◽  
pp. 936-944 ◽  
Author(s):  
Yurong Lai ◽  
Kathleen E. Sampson ◽  
Larissa M. Balogh ◽  
Timothy G. Brayman ◽  
Steven R. Cox ◽  
...  
Keyword(s):  
Clinical Evidence ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Renal Secretion ◽  
Anion Transporter ◽  
Organic Anion Transporter 3 ◽  
Toxin Extrusion

Role of organic anion transporter 3 in the renal excretion of biapenem and potential drug-drug interactions

2021 ◽  
pp. 105814
Author(s):  
Wenyan Li ◽  
Zheng Jiao ◽  
Yanhui Liu ◽  
Jiacheng Yao ◽  
Guodong Li ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Renal Excretion ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Potential Drug ◽  
Anion Transporter ◽  
Organic Anion Transporter 3

Human Organic Anion Transporter 3 Gene Is Regulated Constitutively and Inducibly via a cAMP-Response Element

2006 ◽  
Vol 319 (1) ◽  
pp. 317-322 ◽  
Author(s):  
Ken Ogasawara ◽  
Tomohiro Terada ◽  
Jun-ichi Asaka ◽  
Toshiya Katsura ◽  
Ken-ichi Inui
Keyword(s):  
Organic Anion ◽  
Organic Anion Transporter ◽  
Camp Response Element ◽  
Response Element ◽  
Anion Transporter ◽  
Organic Anion Transporter 3

scholarly journals Impaired Insulin Signaling Affects Renal Organic Anion Transporter 3 (Oat3) Function in Streptozotocin-Induced Diabetic Rats

PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e96236 ◽  
Author(s):  
Anusorn Lungkaphin ◽  
Phatchawan Arjinajarn ◽  
Anchalee Pongchaidecha ◽  
Chutima Srimaroeng ◽  
Lisa Chatsudthipong ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Organic Anion ◽  
Diabetic Rats ◽  
Organic Anion Transporter ◽  
Anion Transporter ◽  
Impaired Insulin ◽  
Organic Anion Transporter 3

Adaptive responses of renal organic anion transporter 3 (OAT3) during cholestasis

2008 ◽  
Vol 295 (1) ◽  
pp. F247-F252 ◽  
Author(s):  
Jiarong Chen ◽  
Tomohiro Terada ◽  
Ken Ogasawara ◽  
Toshiya Katsura ◽  
Ken-ichi Inui
Keyword(s):  
Bile Acids ◽  
Cholic Acid ◽  
Molecular Mechanisms ◽  
Competitive Inhibition ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Specific Substrate ◽  
Renal Secretion ◽  
Sd Rats ◽  
Anion Transporter

During cholestasis, bile acids are mainly excreted into the urine, but adaptive renal responses to cholestasis, especially molecular mechanisms for renal secretion of bile acids, have not been well understood. Organic anion transporters (OAT1 and OAT3) are responsible for membrane transport of anionic compounds at the renal basolateral membranes. In the present study, we investigated the pathophysiological roles of OAT1 and OAT3 in terms of renal handling of bile acids. The Eisai hyperbilirubinemic rats (EHBR), mutant rats without multidrug resistance-associated protein 2, showed higher serum and urinary concentrations of bile acids, compared with Sprague-Dawley (SD) rats (wild type). The protein expression level of rat OAT3 was significantly increased in EHBR compared with SD rats, whereas the expression of rat OAT1 was unchanged. The transport activities of rat and human OAT3, but not OAT1, were markedly inhibited by various bile acids such as chenodeoxycholic acid and cholic acid. Cholic acid, glycocholic acid, and taurocholic acid, which mainly increased during cholestasis, are transported by OAT3. The plasma concentration of β-lactam antibiotic cefotiam, a specific substrate for OAT3, was more increased in EHBR than in SD rats despite upregulation of OAT3 protein. This may be due to the competitive inhibition of cefotiam transport by bile acids via OAT3. In conclusion, the present study clearly demonstrated that OAT3 is responsible for renal secretion of bile acids during cholestasis and that the pharmacokinetic profile of OAT3 substrates may be affected by cholestasis.

scholarly journals Exhaustive exercise decreases renal organic anion transporter 3 function

2018 ◽  
Vol 69 (2) ◽  
pp. 245-251 ◽  
Author(s):  
Tipwadee Bunprajun ◽  
Chaowalit Yuajit ◽  
Rattikarn Noitem ◽  
Varanuj Chatsudthipong
Keyword(s):  
Organic Anion ◽  
Organic Anion Transporter ◽  
Exhaustive Exercise ◽  
Anion Transporter ◽  
Organic Anion Transporter 3

scholarly journals Renal secretion of hydrochlorothiazide involves organic anion transporter 1/3, organic cation transporter 2, and multidrug and toxin extrusion protein 2-K

2019 ◽  
Vol 317 (4) ◽  
pp. F805-F814
Author(s):  
Jia Yin ◽  
David J. Wagner ◽  
Bhagwat Prasad ◽  
Nina Isoherranen ◽  
Kenneth E. Thummel ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Organic Cation ◽  
Organic Anion ◽  
Organic Cation Transporter ◽  
Tubular Secretion ◽  
Organic Anion Transporter ◽  
Anion Transporters ◽  
Anion Transporter ◽  
Organic Cation Transporter 2 ◽  
Toxin Extrusion

Hydrochlorothiazide (HCTZ) is the most widely used thiazide diuretic for the treatment of hypertension either alone or in combination with other antihypertensives. HCTZ is mainly cleared by the kidney via tubular secretion, but the underlying molecular mechanisms are unclear. Using cells stably expressing major renal organic anion and cation transporters [human organic anion transporter 1 (hOAT1), human organic anion transporter 3 (hOAT3), human organic cation transporter 2 (hOCT2), human multidrug and toxin extrusion 1 (hMATE1), and human multidrug and toxin extrusion 2-K (hMATE2-K)], we found that HCTZ interacted with both organic cation and anion transporters. Uptake experiments further showed that HCTZ is transported by hOAT1, hOAT3, hOCT2, and hMATE2-K but not by hMATE1. Detailed kinetic analysis coupled with quantification of membrane transporter proteins by targeted proteomics revealed that HCTZ is an excellent substrate for hOAT1 and hOAT3. The apparent affinities ( Km) for hOAT1 and hOAT3 were 112 ± 8 and 134 ± 13 μM, respectively, and the calculated turnover numbers ( kcat) were 2.48 and 0.79 s−1, respectively. On the other hand, hOCT2 and hMATE2-K showed much lower affinity for HCTZ. The calculated transport efficiency ( kcat/ Km) at the single transporter level followed the rank order of hOAT1> hOAT3 > hOCT2 and hMATE2-K, suggesting a major role of organic anion transporters in tubular secretion of HCTZ. In vitro inhibition experiments further suggested that HCTZ is not a clinically relevant inhibitor for hOAT1 or hOAT3. However, strong in vivo inhibitors of hOAT1/3 may alter renal secretion of HCTZ. Together, our study elucidated the molecular mechanisms underlying renal handling of HCTZ and revealed potential pathways involved in the disposition and drug-drug interactions for this important antihypertensive drug in the kidney.

scholarly journals Rat Organic Anion Transporter 3 and Organic Anion Transporting Polypeptide 1 Mediate Perfluorooctanoic Acid Transport

2007 ◽  
Vol 53 (1) ◽  
pp. 77-83 ◽  
Author(s):  
Masanori Katakura ◽  
Naomi Kudo ◽  
Tadashi Tsuda ◽  
Yasuhide Hibino ◽  
Atsushi Mitsumoto ◽  
...  
Keyword(s):  
Organic Anion ◽  
Perfluorooctanoic Acid ◽  
Organic Anion Transporter ◽  
Acid Transport ◽  
Organic Anion Transporting Polypeptide ◽  
Anion Transporter ◽  
Organic Anion Transporter 3
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