PMID- 22850405 OWN - NLM STAT- MEDLINE DCOM- 20130111 LR - 20211021 IS - 1559-7016 (Electronic) IS - 0271-678X (Print) IS - 0271-678X (Linking) VI - 32 IP - 11 DP - 2012 Nov TI - Transport of biogenic amine neurotransmitters at the mouse blood-retina and blood-brain barriers by uptake1 and uptake2. PG - 1989-2001 LID - 10.1038/jcbfm.2012.109 [doi] AB - Uptake1 and uptake2 transporters are involved in the extracellular clearance of biogenic amine neurotransmitters at synaptic clefts. We looked for them at the blood-brain barrier (BBB) and blood-retina barriers (BRB), where they could be involved in regulating the neurotransmitter concentration and modulate/terminate receptor-mediated effects within the neurovascular unit (NVU). Uptake2 (Oct1-3/Slc22a1-3, Pmat/Slc29a4) and Mate1/Slc47a1 transporters are also involved in the transport of xenobiotics. We used in situ carotid perfusion of prototypic substrates like [(3)H]-1-methyl-4-phenylpyridinium ([(3)H]-MPP(+)), [(3)H]-histamine, [(3)H]-serotonin, and [(3)H]-dopamine, changes in ionic composition and genetic deletion of Oct1-3 carriers to detect uptake1 and uptake2 at the BBB and BRB. We showed that uptake1 and uptake2 are involved in the transport of [(3)H]-dopamine and [(3)H]-MPP(+) at the blood luminal BRB, but not at the BBB. These functional studies, together with quantitative RT-PCR and confocal imaging, suggest that the mouse BBB lacks uptake1 (Net/Slc6a2, Dat/Slc6a3, Sert/Slc6a4), uptake2, and Mate1 on both the luminal and abluminal sides. However, we found evidence for functional Net and Oct1 transporters at the luminal BRB. These heterogeneous transport properties of the brain and retina NVUs suggest that the BBB helps protect the brain against biogenic amine neurotransmitters in the plasma while the BRB has more of a metabolic/endocrine role. FAU - Andre, Pascal AU - Andre P AD - INSERM U705, CNRS UMR 8206, Universite Paris Descartes, Sorbonne Paris Cite, Universite Paris Diderot, Faculte de Pharmacie, Paris, France. FAU - Saubamea, Bruno AU - Saubamea B FAU - Cochois-Guegan, Veronique AU - Cochois-Guegan V FAU - Marie-Claire, Cynthia AU - Marie-Claire C FAU - Cattelotte, Julie AU - Cattelotte J FAU - Smirnova, Maria AU - Smirnova M FAU - Schinkel, Alfred H AU - Schinkel AH FAU - Scherrmann, Jean-Michel AU - Scherrmann JM FAU - Cisternino, Salvatore AU - Cisternino S LA - eng PT - Journal Article DEP - 20120801 PL - United States TA - J Cereb Blood Flow Metab JT - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism JID - 8112566 RN - 0 (Biogenic Amines) RN - 0 (Carrier Proteins) RN - 0 (Membrane Transport Proteins) RN - 0 (Neurotransmitter Agents) RN - 333DO1RDJY (Serotonin) RN - 63231-63-0 (RNA) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Algorithms MH - Animals MH - Biogenic Amines/*metabolism MH - Blood-Brain Barrier/*metabolism MH - Capillaries/metabolism MH - Carrier Proteins/metabolism MH - Cerebral Cortex/blood supply/metabolism MH - Dopamine/metabolism MH - Immunochemistry MH - Immunohistochemistry MH - Kidney/metabolism MH - Male MH - Membrane Transport Proteins/metabolism MH - Mice MH - Microscopy, Confocal MH - Neurons/metabolism MH - Neurotransmitter Agents/*metabolism MH - Polymerase Chain Reaction MH - RNA/biosynthesis MH - Retina/*metabolism MH - Serotonin/metabolism MH - Tissue Distribution PMC - PMC3493996 EDAT- 2012/08/02 06:00 MHDA- 2013/01/12 06:00 PMCR- 2013/11/01 CRDT- 2012/08/02 06:00 PHST- 2012/08/02 06:00 [entrez] PHST- 2012/08/02 06:00 [pubmed] PHST- 2013/01/12 06:00 [medline] PHST- 2013/11/01 00:00 [pmc-release] AID - jcbfm2012109 [pii] AID - 10.1038/jcbfm.2012.109 [doi] PST - ppublish SO - J Cereb Blood Flow Metab. 2012 Nov;32(11):1989-2001. doi: 10.1038/jcbfm.2012.109. Epub 2012 Aug 1.