Extracellular nucleotides have been implicated in a number of physiological functions. Nucleotides act on cell-surface receptors known as P2 receptors, of which several subtypes have been cloned. P2X receptors are ligand-gated ion channels, whereas P2Y receptors belong to the superfamily of G-protein-coupled receptors. The human P2Y-receptor family is composed of seven subtypes (P2Y(1), P2Y(2), P2Y(4), P2Y(6), P2Y(11), P2Y(12), P2Y(13)). The principal physiological agonists of the human P2Y receptors are ADP (P2Y(1), P2Y(12), P2Y(13)), UTP/ATP (P2Y(2)), UTP (P2Y(4)), UDP (P2Y(6)) and ATP (P2Y(11)). P2Y receptors are widely expressed in human tissues, and many subtypes are found in vascular smooth muscle cells and endothelial cells in blood vessels. The intracellular signaling of P2Y receptors is very complex. Activation of P2Y receptors in blood vessels induces vasodilation or vasoconstriction, prolifera- tion of vascular smooth muscle cells and Ca(2+)-sensitization. All mechanisms play an important role in blood pressure control and cardiovascular disease. (c) 2002 Prous Science. All rights reserved.