A new in vitro model for blood-cerebrospinal fluid barrier transport studies: an immortalized choroid plexus epithelial cell line derived from the tsA58 SV40 large T-antigen gene transgenic rat.
The blood-cerebrospinal fluid barrier (BCSFB) plays a key role in the influx and efflux transport of drugs and endogenous substrates in the cerebrospinal fluid (CSF). To clarify the molecular mechanism of the BCSFB transport system, a new in vitro BCSFB model, i.e. an immortalized rat choroid plexus epithelial cell line (TR-CSFB), has been established from transgenic rats harboring a temperature-sensitive simian virus 40 large T-antigen gene. TR-CSFB cells grow well at 33 degrees C because of activation of the temperature-sensitive large T-antigen. These cells have a polygonal epithelial cell morphology and express typical choroid plexus epithelial cell markers, such as transthyretin (TTR) and Na+, K+ -ATPase, as well as the transporters, system A and ABCC1/mrp1. The localization of Na+, K+ -ATPase, and the transport direction of system A are polarized in TR-CSFB cells as is the case in vivo. TR-CSFB cells exhibit L-proline and L-glutamic acid uptake activities and may reflect the CSF-to-blood efflux transport functions involving these amino acids in vivo. Using TR-CSFB cells, we found for the first time that oatp3 is expressed at the BCSFB. TR-CSFB cells appear to be a useful in vitro model of the BCSFB for the study of drug transport, BCSFB transporters, and the regulation of BCSFB functions.
Hosoya
Ken-ichi
K
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Hori
Satoko
S
Ohtsuki
Sumio
S
Terasaki
Tetsuya
T
D000818:Animals; D030801:Animals, Genetically Modified; D000957:Antigens, Viral, Tumor / Q000235:genetics* / Q000502:physiology; D001692:Biological Transport; D001812:Blood-Brain Barrier; D002460:Cell Line; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D002831:Choroid Plexus / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent / Q000502:physiology; D051381:Rats; D013539:Simian virus 40 / Q000276:immunology*
D000957:Antigens, Viral, Tumor; D029362:Organic Anion Transporters, Sodium-Independent; C421143:Slco1a5 protein, rat