Specific receptors for extracellular ATP that recognize the triphosphate nucleotide but not adenosine were first proposed in 1972, on the basis of pharmacological evidence from autonomic neuroeffector cellsL The pharmacological evidence has since been greatly extended and reinforced (reviewed in Refs 2, 3). The existence of these receptors was further strengthened by direct evidence of ATP release at the responsive sites, either in a paracrine mode, for example, in the vascular and immune systems, or from both peripheral and central nerve terminals 4. These receptors are known as P2 purinocepto rs5, and are entirely distinct from the adenosine receptors (or P1 purinoceptors).

The P2 purinoceptor category was further divided 6 pharmacologically into two major classes, P2x and P2Y receptors, and the poorly defined P2z receptor, which forms the large channel system of the mast cell 2. The P2x receptors are members of the transmittergated ion channel superfamily of receptors 7, and have been detected by the direct recording of fast responses to ATP and to their specific agonist c¢,~-methylene-