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Reduced cyclosporin accumulation in multidrug-resistant cells.

Abstract：

:Cyclosporin accumulation was reduced by 50% or more in multidrug- resistant CHRC5 CHO cells with high levels of P-glycoprotein expression compared to drug sensitive AuxB1 CHO cells. This difference could be overcome by verapamil which is known to interact with P-glycoprotein and reverse multidrug resistance. The difference in cyclosporin accumulation between sensitive and resistant cells decreased with increasing cyclosporin concentrations suggesting that cyclosporine itself regulated its own accumulation through interaction with P-glycoprotein. Indeed, cyclosporin also reversed differences in vinblastine accumulation between resistant and sensitive cell lines. Since P-glycoprotein is highly expressed in the kidney which is also a target for cyclosporin toxicity, the effects of verapamil on cyclosporin accumulation were studied in two renal cell lines, rat mesangial cells and LLCPK1, cells. Verapamil increased cyclosporin accumulation by approximately 70%. These results suggest that cellular cyclosporine accumulation is regulated at least in part by its interaction with P-glycoprotein.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Goldberg H,Ling V,Wong PY,Skorecki K

doi

10.1016/s0006-291x(88)80073-1

subject

Has Abstract

pub_date

1988-04-29 00:00:00

pages

552-8

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(88)80073-1

journal_volume

152

pub_type

杂志文章

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