Identity of the Organic Cation Transporter OCT3 as the Extraneuronal Monoamine Transporter (uptake2) and Evidence for the Expression of the Transporter in the Brain

摘要: Abstract We investigated the transport of cationic neurotoxins and neurotransmitters by potential-sensitive organic transporter OCT3 its steroid sensitivity using heterologous expression systems also analyzed in brain. When expressed mammalian cells, mediates uptake neurotoxin 1-methyl-4-phenylpyridinium (MPP+) neurotransmitter dopamine. Competition experiments show that several neuroactive agents including amphetamines interact with OCT3. Xenopus laevis oocytes, OCT3-mediated MPP+ is associated inward currents under voltage-clamp conditions. The MPP+-induced are saturable respect to concentration, half-maximal saturation (K 0.5) occurs at about 25 μm membrane potential clamped −50 mV. K 0.5 for markedly influenced potential. inhibited steroids, β-estradiol most potent inhibitor i ∼1 μm). pattern different from OCT1 OCT2 but correlates significantly extraneuronal monoamine (uptake2). characteristics provide strong evidence molecular identity as uptake2. brain evidenced Northern blot analysis, reverse transcription-polymerase chain reaction, situ hybridization OCT3-specific probes. transcript hybridizing probe has been established sequencing reaction product isolation cDNA a library. Regional distribution studies widely regions, especially hippocampus, cerebellum, cerebral cortex. likely play significant role disposition