Therapeutic drugs modulate ATP-Binding cassette transporter-mediated transport of amyloid beta(1-42) in brain microvascular endothelial cells.

Therapeutic drugs modulate ATP-Binding cassette transporter-mediated transport of amyloid beta(1-42) in brain microvascular endothelial cells. Eur J Pharmacol. 2020 Feb 13;:173009 Authors: Shubbar MH, Penny JI Abstract Deposition of amyloid-β peptide (Aβ(1-42)) is a hallmark of Alzheimer's disease. Clearance of Aβ(1-42), across the blood-brain barrier (BBB), is mediated by ATP-binding Cassette (ABC) efflux transporters. Many therapeutic drugs inhibit ABC transporters, but little is known of the effect of therapeutic drugs on Aβ(1-42) transport across BBB endothelial cells. The effects of selected, widely prescribed, therapeutic drugs on ABCB1, ABCC5 and ABCG2 activities were determined by measuring intracellular levels of calcein, GS-MF, and Hoechst 33342 respectively in primary porcine brain endothelial cells (PBECs). The ability of ABCB1, ABCC5 and ABCG2 to transport Aβ(1-42) was determined using fluorescent Aβ(1-42). The ability of the ABCB1, ABCC5 and ABCG2 inhibitor telmisartan to modify transcellular Aβ(1-42) transport was investigated using PBEC monolayers housed in Transwell® inserts. Treatment of PBECs with ABC transporter inhibitory drugs (indomethacin, olanzapine, chlorpromazine, telmisartan, pantoprazole, quinidine, sulfasalazine and nefazodone) increased Aβ(1-42) intracellular accumulation. Inhibition of ABCB1, ABCC5 and ABCG2 by telmisartan increased Aβ(1-42) transport in the apical to basal direction and redu...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research