Substrates of the Human Brain Proton-Organic Cation Antiporter and Comparison with Organic Cation Transporter 1 Activities.
blood–brain barrier
hCMEC/D3 cells
organic cation transporter
orphan transporter
proton-organic cation antiporter
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
29 Jul 2022
29 Jul 2022
Historique:
received:
30
06
2022
revised:
18
07
2022
accepted:
26
07
2022
entrez:
12
8
2022
pubmed:
13
8
2022
medline:
16
8
2022
Statut:
epublish
Résumé
Many organic cations (OCs) may be transported through membranes by a genetically still uncharacterized proton-organic cation (H + OC) antiporter. Here, we characterized an extended substrate spectrum of this antiporter. We studied the uptake of 72 drugs in hCMEC/D3 cells as a model of the human blood-brain barrier. All 72 drugs were tested with exchange transport assays and the transport of 26 of the drugs was studied in more detail concerning concentration-dependent uptake and susceptibility to specific inhibitors. According to exchange transport assays, 37 (51%) drugs were good substrates of the H + OC antiporter. From 26 drugs characterized in more detail, 23 were consistently identified as substrates of the H + OC antiporter in six different assays and transport kinetic constants could be identified with intrinsic clearances between 0.2 (ephedrine) and 201 (imipramine) mL × minute
Identifiants
pubmed: 35955563
pii: ijms23158430
doi: 10.3390/ijms23158430
pmc: PMC9369162
pii:
doi:
Substances chimiques
Antiporters
0
Cations
0
Octamer Transcription Factor-1
0
Organic Cation Transport Proteins
0
Organic Cation Transporter 1
0
POU2F1 protein, human
0
Protons
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : 461080000, SA
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