Roles of P2-purinoceptors in the cardiovascular system

Characterization of P2-purinoceptor subtypes has facilitated understanding of the many diverse effects produced by purine nucleotides. P2X-Purinoceptors are located on vascular smooth muscle where they mediate vasoconstriction resulting from ATP released as a cotransmitter with noradrenaline from sympathetic nerves. P2Y-Purinoceptors are usually located on the vascular endothelium where they have a role as mediators of vascular relaxation by locally produced ATP. In some vessels, P2Y-purinoceptors are also located on the smooth muscle, perhaps in association with purinergic or sensory nerves, where they can elicit direct relaxation to neuronally released ATP. The net effect of ATP and its analogues on isolated vessels or on vascular beds will be the results of actions mediated by P2X- and P2Y-purinoceptor subtypes, although changes in vascular tone and in integrity of nerves and endothelial cells may alter the balance of the response. Such changes have been observed in diseased states (e.g., atherosclerosis) and may have important implications for the involvement of P2-purinoceptors in, for example, vasospasm. The development of selective and potent antagonists to P2X- and P2Y-purinoceptors has so far remained elusive, and their therapeutic potential can only be guessed.