CJZ3, a lomerizine derivative, modulates P-glycoprotein function in rat brain microvessel endothelial cells.
OBJECTIVE
To investigate the modulatory effect of CJZ3, a lomerizine derivative, on P-glycoprotein (P-gp) function in rat brain microvessel endothelial cells (RBMEC).


METHODS
RBMEC were isolated and cultured in Dulbecco modified Eagle medium/F12 (1:1) medium, and the amount of intracellular rhodamine 123 (Rh123) was determined using a fluorescence spectrophotometer to evaluate the modulatory effect of CJZ3 on P-gp function.


RESULTS
The accumulation of Rh123 was potentiated in a concentration-dependent manner after incubation with CJZ3 for RBMEC, but not for human umbilical vein endothelial cells (HUVEC). CJZ3 caused the accumulation of intracellular Rh123 in a time-dependent manner and significantly decreased the efflux of Rh123 from the cells. The inhibitory effect of CJZ3 on P-gp function was reversible and remained for 120 min after CJZ3 (2.5 micromol/L) was removed from the medium.


CONCLUSIONS
CJZ3 has a potent in vitro effect on the inhibition of P-gp function.
Ji
Bian-Sheng
BS
Institute of Pharmacy, Henan University, Kaifeng 475001, China.
He
Ling
L
Li
Xiao-Qu
XQ
Liu
Guo-Qing
GQ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000098:blood supply*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008833:Microcirculation / Q000166:cytology; D015394:Molecular Structure; D010879:Piperazines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020112:Rhodamine 123 / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002121:Calcium Channel Blockers; D010879:Piperazines; D020112:Rhodamine 123; C052424:lomerizine