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 ◽  
...  
2003 ◽  
Vol 23 (4) ◽  
pp. 432-440 ◽  
Author(s):  
Shinobu Mori ◽  
Hitomi Takanaga ◽  
Sumio Ohtsuki ◽  
Tsuneo Deguchi ◽  
Young-Sook Kang ◽  
...  

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.


PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e96236 ◽  
Author(s):  
Anusorn Lungkaphin ◽  
Phatchawan Arjinajarn ◽  
Anchalee Pongchaidecha ◽  
Chutima Srimaroeng ◽  
Lisa Chatsudthipong ◽  
...  

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