Document Detail

Stereoselective regulation of MDR1 expression in Caco-2 cells by cetirizine enantiomers.
MedLine Citation:
PMID:  17394131     Owner:  NLM     Status:  MEDLINE    
MDR1-encoded P-glycoprotein (P-gp) is a drug efflux transporter mainly expressed in liver, kidney, intestine, brain (at the level of the blood-brain barrier), and placenta. It thus plays important roles in drug absorption, distribution, and excretion. Cetirizine is a second-generation nonsedating antihistamine used to treat allergic disease of respiratory system, skin and eyes. To evaluate P-gp expression and function in Caco-2 cells pretreated with cetirizine enantiomers, we assessed the sensitivity of Caco-2 cells to paclitaxel using the MTT assay and the polarized transport of rhodamine-123 and doxorubicin across Caco-2 monolayers. RT-PCR and flow cytometry were used to assay MDR1 mRNA and P-gp protein respectively. The sensitivity of Caco-2 cells to paclitaxel decreased significantly after cells were pretreated with 100 microM R-cetirizine but increased upon treatment with S-cetirizine. The efflux of rhodamine-123 and doxorubicin was enhanced significantly after Caco-2 monolayers were pretreated with 100 microM R-cetirizine but was reduced by S-cetirizine. The MDR1 mRNA and P-gp levels in Caco-2 cells were increased by 100 microM R-cetirizine and decreased by 100 microM S-cetirizine. These results suggest that R-cetirizine up-regulates MDR1 expression while S-cetirizine down-regulates MDR1 expression.
Shuijie Shen; Ying He; Su Zeng
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Chirality     Volume:  19     ISSN:  0899-0042     ISO Abbreviation:  Chirality     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-04-30     Completed Date:  2007-09-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8914261     Medline TA:  Chirality     Country:  United States    
Other Details:
Languages:  eng     Pagination:  485-90     Citation Subset:  IM    
Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
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MeSH Terms
Biological Transport
Caco-2 Cells
Cetirizine / chemistry*,  pharmacology*
Dose-Response Relationship, Drug
Drug Interactions
Drug Resistance, Neoplasm
Flow Cytometry
Gene Expression Regulation, Neoplastic*
Histamine H1 Antagonists, Non-Sedating / pharmacology*
P-Glycoprotein / biosynthesis*,  chemistry,  physiology*
P-Glycoproteins / metabolism
Paclitaxel / pharmacology
Rhodamine 123 / pharmacology
Reg. No./Substance:
0/Histamine H1 Antagonists, Non-Sedating; 0/P-Glycoprotein; 0/P-Glycoproteins; 33069-62-4/Paclitaxel; 62669-70-9/Rhodamine 123; 83881-51-0/Cetirizine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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