Role of blood-brain barrier organic anion transporter 3 (OAT3) in the efflux of indoxyl sulfate, a uremic toxin: its involvement in neurotransmitter metabolite clearance from the brain

2002 ◽  
Vol 83 (1) ◽  
pp. 57-66 ◽  
Author(s):  
Sumio Ohtsuki ◽  
Hiroshi Asaba ◽  
Hitomi Takanaga ◽  
Tsuneo Deguchi ◽  
Ken-ichi Hosoya ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Indoxyl Sulfate ◽  
Uremic Toxin ◽  
Anion Transporter ◽  
Metabolite Clearance ◽  
Organic Anion Transporter 3 ◽  
The Brain

scholarly journals Major role of organic anion transporter 3 in the transport of indoxyl sulfate in the kidney

2002 ◽  
Vol 61 (5) ◽  
pp. 1760-1768 ◽  
Author(s):  
Tsuneo Deguchi ◽  
Sumio Ohtsuki ◽  
Masaki Otagiri ◽  
Hitomi Takanaga ◽  
Hiroshi Asaba ◽  
...  
Keyword(s):  
Organic Anion ◽  
Organic Anion Transporter ◽  
Indoxyl Sulfate ◽  
Anion Transporter ◽  
Organic Anion Transporter 3

Rat Organic Anion Transporter 3 (rOAT3) is Responsible for Brain-to-Blood Efflux of Homovanillic Acid at the Abluminal Membrane of Brain Capillary Endothelial Cells

2003 ◽  
Vol 23 (4) ◽  
pp. 432-440 ◽  
Author(s):  
Shinobu Mori ◽  
Hitomi Takanaga ◽  
Sumio Ohtsuki ◽  
Tsuneo Deguchi ◽  
Young-Sook Kang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Homovanillic Acid ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Indoxyl Sulfate ◽  
Brain Capillary ◽  
Anion Transporter ◽  
Capillary Endothelial Cells ◽  
Organic Anion Transporter 3 ◽  
The Brain

The mechanism that removes homovanillic acid (HVA), an end metabolite of dopamine, from the brain is still poorly understood. The purpose of this study is to identify and characterize the brain-to-blood HVA efflux transporter at the rat blood–brain barrier (BBB). Using the Brain Efflux Index method, the apparent in vivo efflux rate constant of [3H]HVA from the brain, keff, was determined to be 1.69 × 10–2 minute–1. This elimination was significantly inhibited by para-aminohippuric acid (PAH), benzylpenicillin, indoxyl sulfate, and cimetidine, suggesting the involvement of rat organic anion transporter 3 (rOAT3). rOAT3-expressing oocytes exhibited [3H]HVA uptake (Km = 274 μmol/L), which was inhibited by several organic anions, such as PAH, indoxyl sulfate, octanoic acid, and metabolites of monoamine neurotransmitters. Neurotransmitters themselves did not affect the uptake. Furthermore, immunohistochemical analysis suggested that rOAT3 is localized at the abluminal membrane of brain capillary endothelial cells. These results provide the first evidence that rOAT3 is expressed at the abluminal membrane of the rat BBB and is involved in the brain-to-blood transport of HVA. This HVA efflux transport system is likely to play an important role in controlling the level of HVA in the CNS.

scholarly journals Organic anion transporter 3 is involved in the brain-to-blood efflux transport of thiopurine nucleobase analogs

2004 ◽  
Vol 90 (4) ◽  
pp. 931-941 ◽  
Author(s):  
Shinobu Mori ◽  
Sumio Ohtsuki ◽  
Hitomi Takanaga ◽  
Tazuru Kikkawa ◽  
Young-Sook Kang ◽  
...  
Keyword(s):  
Organic Anion ◽  
Organic Anion Transporter ◽  
Efflux Transport ◽  
Anion Transporter ◽  
Organic Anion Transporter 3 ◽  
The Brain

Role of organic anion transporter 3 (Oat3) in the renal transport of glutathione (GSH)

2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Lawrence H. Lash ◽  
David A. Putt ◽  
Feng Xu ◽  
Larry H. Matherly
Keyword(s):  
Organic Anion ◽  
Organic Anion Transporter ◽  
Renal Transport ◽  
Anion Transporter ◽  
Organic Anion Transporter 3

scholarly journals Remote sensing and signaling in kidney proximal tubules stimulates gut microbiome-derived organic anion secretion

2019 ◽  
Vol 116 (32) ◽  
pp. 16105-16110 ◽  
Author(s):  
Jitske Jansen ◽  
Katja Jansen ◽  
Ellen Neven ◽  
Ruben Poesen ◽  
Amr Othman ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Gut Microbiome ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Indoxyl Sulfate ◽  
Regulation Mechanism ◽  
Uremic Toxin ◽  
Proximal Tubule Cell ◽  
Anion Secretion ◽  
Anion Transporter

Membrane transporters and receptors are responsible for balancing nutrient and metabolite levels to aid body homeostasis. Here, we report that proximal tubule cells in kidneys sense elevated endogenous, gut microbiome-derived, metabolite levels through EGF receptors and downstream signaling to induce their secretion by up-regulating the organic anion transporter-1 (OAT1). Remote metabolite sensing and signaling was observed in kidneys from healthy volunteers and rats in vivo, leading to induced OAT1 expression and increased removal of indoxyl sulfate, a prototypical microbiome-derived metabolite and uremic toxin. Using 2D and 3D human proximal tubule cell models, we show that indoxyl sulfate induces OAT1 via AhR and EGFR signaling, controlled by miR-223. Concomitantly produced reactive oxygen species (ROS) control OAT1 activity and are balanced by the glutathione pathway, as confirmed by cellular metabolomic profiling. Collectively, we demonstrate remote metabolite sensing and signaling as an effective OAT1 regulation mechanism to maintain plasma metabolite levels by controlling their secretion.

scholarly journals Role of rat organic anion transporter 3 (Oat3) in the renal basolateral transport of glutathione

2007 ◽  
Vol 170 (2) ◽  
pp. 124-134 ◽  
Author(s):  
Lawrence H. Lash ◽  
David A. Putt ◽  
Feng Xu ◽  
Larry H. Matherly
Keyword(s):  
Organic Anion ◽  
Organic Anion Transporter ◽  
Anion Transporter ◽  
Organic Anion Transporter 3
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