Effects of novel tetrahydroisoquinoline derivative-H108 on activity of P-glycoprote in virto and injury of PC12 cells

Abstract

Abstract: AIM: To observe the effects of H108, a novel tetrahydroisoquinoline derivative on the drug efflux activity of P-glycoprotein (P-gp) on K562/ADR and rat brain microvessel endothelial cells (RBMECs), and the protective effects on the injury of PC12 cells.METHODS: Fluorescence substrate of P-gp rhodamine123 (Rh123) was used to examine the effects of H108 on the drug efflux activity of P-gp on K562/ADR and RBMECs. The viability of PC12 cells was studied by MTT assay to assess the protective effect of H108 on the injury of PC12 cells that were induced by sodium dithionite (Na₂S₂O₄), sodium nitroprusside (SNP) and hydrogen peroxide (H₂O₂).RESULTS: H108 increased the intracellular accumulation of Rh123 in a dose-dependent manner in RBMECs and K562/ADR.The viability rate of PC12 cells injuried by SNP and Na₂S₂O₄ increased significantly when pretreated with H108.CONCLUSION: H108 has relatively potent P-gp reversal activity, and exhibits potential protective effects on neurons.It can be developed as a novel and potent P-gp reverser, particularly acting on Pgp of BBB.

Key words: tetrahydroisoquinoline, P-glycoprotein, multidrug resistance, K562/ADR, rat brain microvessel endothelial cells, PC12 cells

CLC Number:

R965.1

YANG Zhi-Yong, LIU Guo-Qing, HUANG Wen-Long¹. Effects of novel tetrahydroisoquinoline derivative-H108 on activity of P-glycoprote in virto and injury of PC12 cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(3): 275-280.

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