Confocal imaging of xenobiotic transport across the choroid plexus

Abstract

Confocal microscopy is a tool by which the distribution of fluorescent compounds within living, complex tissues can be mapped at submicrometer resolution and quantitated. This laboratory has used confocal imaging and quantitative image analysis to visualize transport of xenobiotics across intact rat and mouse choroid plexus. For both organic anions and organic cations, transport from CSF to blood is a three-step process involving: uptake at the apical membrane of the epithelial cells, transcellular transport and efflux at the basolateral membrane. Both transmembrane steps are carrier-mediated and concentrative. In the cytoplasm of the epithelial cells, all fluorescent xenobiotics studied partition between diffuse and punctate compartments, some of which appear to be mobile. Use of confocal imaging in combination with transport inhibitors, treatments that alter metabolism and ion gradients and tissue from genetically altered mice, has allowed us to characterize transport at specific membrane sites and begin to identify the responsible transporters at the molecular level.