Endothelial and epithelial cells are both barriers and bridges between different compartments. This contribution discusses the general principles of paracellular, transcellular, and transmembrane transport with special emphasis on the relation between asymmetry and net movement of small solutes. Asymmetry of cell membrane transport properties is found in both epithelial and endothelial cell layers and provides the basis for transcellular transport. Furthermore, the asymmetry of membrane transporters such as the blood-brain barrier GLUT1 and the renal sodium-glutamate cotransporter is discussed with regard to their different properties at the extra- and intracellular face. These molecular asymmetries play an important role in the efficiency, direction, and regulation of transport processes across the plasma membranes in endothelial and epithelial cells.

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