ABCC1: a gateway for pharmacological compounds to the ischaemic brain

摘要: By preventing access of drugs to the CNS, blood-brain barrier hampers developments in brain pharmacotherapy. Strong efforts are currently being made identify that accumulate more efficaciously ischaemic tissue. We identified an ATP-binding cassette (ABC) transporter, ABCC1, which is expressed on abluminal surface capillary endothelium and mildly downregulated response focal cerebral ischaemia, induced by intraluminal middle artery occlusion. In biodistribution studies we show ABCC1 promotes accumulation known neuroprotective neurotoxic compounds non-ischaemic brain, deactivation reducing tissue concentrations up two orders magnitude. As such, ABCC1's expression functionality differs from liver, spleen testis, where strongly parenchymal cells, resulting -- case liver testis directed transport into blood. After abolished efficacy both compounds. Our data indicate acts as gateway for pharmacological stroke brain. suggest tailoring binding but not luminal ABC transporters may facilitate