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.
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Mori S, Takanaga H, Ohtsuki S, Deguchi T, Kang YS, Hosoya K, Terasaki T
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.
J Cereb Blood Flow Metab. 2003 Apr;23(4):432-40.
- PubMed ID
- 12679720 [ View in PubMed]
- Abstract
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, k(eff), was determined to be 1.69 x 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 (K(m) = 274 micromol/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.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Aminohippuric acid Solute carrier family 22 member 8 Protein Humans UnknownSubstrateInhibitorDetails Benzylpenicillin Solute carrier family 22 member 8 Protein Humans UnknownSubstrateInhibitorDetails Cimetidine Solute carrier family 22 member 8 Protein Humans UnknownSubstrateInhibitorDetails Conjugated estrogens Solute carrier family 22 member 8 Protein Humans UnknownSubstrateInhibitorDetails Indomethacin Solute carrier family 22 member 8 Protein Humans UnknownInhibitorDetails Mercaptopurine Solute carrier family 22 member 8 Protein Humans UnknownSubstrateInhibitorDetails Probenecid Solute carrier family 22 member 8 Protein Humans UnknownInhibitorDetails