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Transport of biogenic amine neurotransmitters at the mouse blood-retina and blood-brain barriers by uptake1 and uptake2.
- Source :
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Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism [J Cereb Blood Flow Metab] 2012 Nov; Vol. 32 (11), pp. 1989-2001. Date of Electronic Publication: 2012 Aug 01. - Publication Year :
- 2012
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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.
- Subjects :
- Algorithms
Animals
Capillaries metabolism
Carrier Proteins metabolism
Cerebral Cortex blood supply
Cerebral Cortex metabolism
Dopamine metabolism
Immunochemistry
Immunohistochemistry
Kidney metabolism
Male
Membrane Transport Proteins metabolism
Mice
Microscopy, Confocal
Neurons metabolism
Polymerase Chain Reaction
RNA biosynthesis
Serotonin metabolism
Tissue Distribution
Biogenic Amines metabolism
Blood-Brain Barrier metabolism
Neurotransmitter Agents metabolism
Retina metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1559-7016
- Volume :
- 32
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 22850405
- Full Text :
- https://doi.org/10.1038/jcbfm.2012.109