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Permeation of Dopamine Sulfate through the Blood-Brain Barrier
- Source :
- PLoS ONE, Vol 10, Iss 7, p e0133904 (2015), PLoS ONE
- Publication Year :
- 2015
-
Abstract
- Dopamine sulfate (DA-3- and DA-4-S) have been determined in the human brain, but it is unclear whether they are locally formed in the central nervous system (CNS), or transported into the CNS from peripheral sources. In the current study, permeation of the blood-brain barrier (BBB) by DA-S was studied by injecting C-13(6)-labelled regioisomers of DA-S ((13)DA-3-S and (13)DA-4-S) and dopamine (DA) subcutaneously (s.c.) in anesthetized rats, then analyzing brain microdialysis and plasma samples by UPLC-MS/MS. The results in the microdialysis samples demonstrated that brain concentrations of (13)DA-S regioisomers clearly increased after the s.c. injections. The concentration of DA did not change, indicating the permeation of DA-S through an intact BBB. The analysis of plasma samples, however, showed that DA-S only permeates the BBB to a small extent, as the concentrations in plasma were substantially higher than in the microdialysis samples. The results also showed that the concentrations of DA-3-S were around three times higher than the concentrations of DA-4-S in rat brain, as well as in the plasma samples after the s.c. injections, indicating that DA-3-S and DA-4-S permeate the BBB with similar efficiency. The fate of (13)DA-S in brain was followed by monitoring C-13(6)-labelled DA-S hydrolysis products, i.e. (13)DA and its common metabolites; however, no C-13(6)-labelled products were detected. This suggests that DA-S either permeates through the BBB back to the peripheral circulation or is dissociated or metabolized by unexpected mechanisms.
- Subjects :
- Microdialysis
PREGNENOLONE SULFATE
Dopamine
Central nervous system
lcsh:Medicine
Pharmacology
Blood–brain barrier
RAT-BRAIN
ISOFLURANE ANESTHESIA
Permeability
5-HYDROXYTRYPTAMINE
IN-VIVO MICRODIALYSIS
chemistry.chemical_compound
Tandem Mass Spectrometry
medicine
Animals
Rats, Wistar
TANDEM MASS-SPECTROMETRY
lcsh:Science
Chromatography, High Pressure Liquid
Brain Chemistry
MOUSE-BRAIN
Multidisciplinary
Sulfates
Chemistry
lcsh:R
SEROTONIN
Brain
Human brain
Permeation
PERFORMANCE LIQUID-CHROMATOGRAPHY
Rats
medicine.anatomical_structure
Blood-Brain Barrier
317 Pharmacy
lcsh:Q
Pregnenolone sulfate
Drug metabolism
Research Article
medicine.drug
MONOAMINE METABOLITES
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- PLoS ONE, Vol 10, Iss 7, p e0133904 (2015), PLoS ONE
- Accession number :
- edsair.doi.dedup.....f4aeb4a4ea696f2db0cc2f2ffd2d2d73