Extracellular purines in endothelial cell barrier regulation

The vascular endothelium is a semi-selective diffusion barrier that regulates a variety of functions including controlling of the passage of macromolecules and fluid between the blood and interstitial fluid. It is well known that loss of this barrier (permeability increase) results in tissue inflammation, the hall mark of inflammatory diseases such as acute lung injury (ALI) and a severe form of it, acute respiratory distress syndrome (ARDS). Apart from ventilation strategies, no standard treatment exists for ALI and ARDS, making the search for novel regulators of endothelial hyperpermeability and dysfunction important. Accumulating data suggest that extracellular purines are promising and physiologically relevant barrier-protective agents. Purines decrease transendothelial permeability by interacting with cell surface P1 and P2Y purinoceptors belonging to the superfamily of G-protein-coupled receptors (GPCR). Selective activation of endothelial purinoreceptors responsible for barrier protection might form a basis for the treatment of various disorders. The therapeutic potential of purinoreceptors is rapidly expanding field in pharmacology and some selective agonists became recently available. In this review, we demonstrate the comprehensive overview of the purinoceptors expression in the endothelium, their interaction with G-proteins and activation of various signal transduction pathways, which lead to an endothelial barrier enhancement and protection.