論文 - 詳細
| RRC ID | 36768 |
|---|---|
| 著者 | Verstraelen J, Reichl S. |
| タイトル | Upregulation of P-glycoprotein expression by ophthalmic drugs in different corneal in-vitro models. |
| ジャーナル | J Pharm Pharmacol |
| Abstract |
OBJECTIVES:The purpose of this study was to analyse P-glycoprotein (P-gp) expression in different human in-vitro cornea models (HCE-T epithelial model and Hemicornea construct) after stimulation with P-gp substrates (rhodamine 123, levofloxacin and acebutolol). METHODS:The influence of P-gp substrates on mRNA expression was analysed using reverse transcriptase polymerase chain reaction (PCR) and real-time PCR. The effect of stimulation on the transporter functionality was estimated with a digoxin efflux assay. The Caco-2 cell line was used as positive control. KEY FINDINGS:The reverse transcriptase PCR results showed an increase in band intensity compared with the control medium for all substrates. The real-time PCR for the Caco-2 and HCE-T epithelial model yielded a similar outcome, in which all tested substrates upregulated P-gp. In contrast, the Hemicornea construct showed no significant increase in the mRNA expression after stimulation. Both in-vitro models possessed similar drug transport profiles after stimulation. A significantly increased efflux of digoxin was measured after 24 and 72 h of stimulation with levofloxacin and acebutolol. CONCLUSIONS:The expression and functionality of the P-gp in corneal tissue can be influenced through time exposure with specific substrates. However, the exact mechanism still requires further elucidation. |
| 巻・号 | 67(5) |
| ページ | 605-15 |
| 公開日 | 2015-5-1 |
| DOI | 10.1111/jphp.12357 |
| PMID | 25643948 |
| MeSH | ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis* Acebutolol / pharmacology* Cells, Cultured Cornea / drug effects* Cornea / metabolism* Humans In Vitro Techniques Levofloxacin / pharmacology* Ophthalmic Solutions / pharmacology* Rhodamine 123 / pharmacology Up-Regulation / drug effects* |
| IF | 2.571 |
| 引用数 | 3 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| リソース情報 | |
| ヒト・動物細胞 | HCE-T(RCB2280) |