Blood-brain and retinal barriers show dissimilar ABC transporter impacts and concealed effect of P-glycoprotein on a novel verapamil influx carrier.

ABSTRACT:

Background and purpose

The respective impact and interplay between ABC (P-glycoprotein/P-gp/Abcb1a, BCRP/ABCG2, MRP/ABCC) and SLC transporter functions at the blood-brain barrier (BBB) and blood-retinal barriers (BRB) are incompletely understood.

Experimental approach

We measured the initial cerebral and retinal distribution of selected ABC substrates by in situ carotid perfusion using P-gp/Bcrp knockout mice and chemical ABC/SLC modulation strategies. P-gp, Bcrp, Mrp1 and Mrp4 were studied by confocal retina imaging.

Key results

Chemical or physical disruption of P-gp increased [(3) H]-verapamil transport by ~10-fold at the BBB and ~1.5-fold at the BRB. [(3) H]-Verapamil transport involved influx-mediated by an organic cation clonidine-sensitive/diphenhydramine-sensi

SUBMITTER: Chapy H 

PROVIDER: S-EPMC4728421 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature