Pharmaceutical research · 2025
Expression and Functional Evaluation of ABC and SLC Transporters in Human Choroid Plexus Papilloma (HIBCPP) Cells: A Human Blood-Cerebrospinal Fluid Barrier Model.
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Kurosawa Toshiki, Ohtsuki Sumio, Ishikawa Hiroshi, Schroten Horst, Schwerk Christian, Kubo Yoshiyuki, Deguchi Yoshiharu
Аннотация
PURPOSE: Human choroid plexus papilloma (HIBCPP) cells derived from choroid plexus papilloma in the lateral ventricle are considered suitable model cells for the blood-cerebrospinal fluid barrier (BCSFB). Therefore, in this study, the transporters expressed in HIBCPP cells were identified, and the functions of representative transporters were evaluated.
METHODS: Transporter protein and mRNA expression were analyzed in HIBCPP cells using quantitative proteomics and quantitative reverse transcription-PCR. Transporter functions were evaluated by cellular uptake and transcellular transport studies using typical substrates.
RESULTS: The following solute carrier (SLC) and ATP-binding cassette (ABC) transporters involved in drug and nutrient transport were expressed in HIBCPP cells: glucose transporter 1 (GLUT1), monocarboxylate transporter 1 (MCT1), L-type amino acid transporter 1 (LAT1), cationic amino acid transporter 1 (CAT1), glutamate transporter (GLAST), SLC35F2, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP). Furthermore, the mRNA of organic anion/cation transporters, such as organic anion transporting polypeptide 1B3 (OATP1B3) and plasma membrane monoamine transporter (PMAT), were detected. Additionally, uptake of representative substrates of the SLC transporters LAT1, CAT1, GLAST, GLUT1, MCT1, and SLC35F2 in HIBCPP cells occurred in a time- and temperature-dependent manner and decreased in the presence of specific inhibitors. Furthermore, the representative substrates of these transporters were transported in a symmetric or asymmetric manner through HIBCPP cells between the apical (cerebrospinal fluid [CSF]) and basolateral (blood) sides.
CONCLUSION: Various nutrient and drug transporters are functionally expressed in HIBCPP cells. Therefore, HIBCPP cells could serve as a useful human BCSFB model to evaluate nutrient and drug transport between the CSF and blood.
METHODS: Transporter protein and mRNA expression were analyzed in HIBCPP cells using quantitative proteomics and quantitative reverse transcription-PCR. Transporter functions were evaluated by cellular uptake and transcellular transport studies using typical substrates.
RESULTS: The following solute carrier (SLC) and ATP-binding cassette (ABC) transporters involved in drug and nutrient transport were expressed in HIBCPP cells: glucose transporter 1 (GLUT1), monocarboxylate transporter 1 (MCT1), L-type amino acid transporter 1 (LAT1), cationic amino acid transporter 1 (CAT1), glutamate transporter (GLAST), SLC35F2, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP). Furthermore, the mRNA of organic anion/cation transporters, such as organic anion transporting polypeptide 1B3 (OATP1B3) and plasma membrane monoamine transporter (PMAT), were detected. Additionally, uptake of representative substrates of the SLC transporters LAT1, CAT1, GLAST, GLUT1, MCT1, and SLC35F2 in HIBCPP cells occurred in a time- and temperature-dependent manner and decreased in the presence of specific inhibitors. Furthermore, the representative substrates of these transporters were transported in a symmetric or asymmetric manner through HIBCPP cells between the apical (cerebrospinal fluid [CSF]) and basolateral (blood) sides.
CONCLUSION: Various nutrient and drug transporters are functionally expressed in HIBCPP cells. Therefore, HIBCPP cells could serve as a useful human BCSFB model to evaluate nutrient and drug transport between the CSF and blood.