title: Transport of biogenic amine neurotransmitters at the mouse blood-retina and blood-brain barriers by uptake1 and uptake2.
abstract: 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.
authors: INSERM U705, CNRS UMR 8206, Université Paris Descartes, Sorbonne Paris Cité, Université Paris Diderot, Faculté de Pharmacie, Paris, France.
authors: Pascal
authors: P
authors: André
authors: Bruno
authors: B
authors: Saubaméa
authors: Véronique
authors: V
authors: Cochois-Guégan
authors: Cynthia
authors: C
authors: Marie-Claire
authors: Julie
authors: J
authors: Cattelotte
authors: Maria
authors: M
authors: Smirnova
authors: Alfred H
authors: AH
authors: Schinkel
authors: Jean-Michel
authors: JM
authors: Scherrmann
authors: Salvatore
authors: S
authors: Cisternino
mesh_terms: D000465:Algorithms; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002196:Capillaries / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D007120:Immunochemistry; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000096:biosynthesis; D012160:Retina / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D001679:Biogenic Amines; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D018377:Neurotransmitter Agents; D012701:Serotonin; D012313:RNA; D004298:Dopamine