The Phospholipase C Linked P2y-Purinergic Receptor

The physiological effects of extracellular ATP and ADP have been broadly described for both the central nervous system and peripheral tissues (Burnstock, 1978; Burnstock and Kennedy, 1986; Gordon, 1986; Williams, 1987; Fleetwood and Gordon, 1987). In contrast to the clearly defined subtypes of P1-purinergic receptors (A1- and A2-receptors) responsible for the physiological effects of extracellular adenosine (Londos and Wolff, 1977; Van Calker, et al., 1979; Stiles, 1986). Subclassification of the ATP- and ADP-regulated P2-purinergic receptors has proven more difficult. No good antagonists of P2-purinergic receptors are available, and cell surface hydrolases metabolize ATP and ADP to adenosine, which could produce variable tissue-dependent effects through P1-purinergic receptors. In spite of these problems some progress in subclassification of P2-purinergic receptors has been made. The observation of differential effects of a large number of ATP and ADP analogs led Burnstock and Kennedy (1985) to propose that two subypes of P2-purinergic receptors exist. P2X-purinergic receptors were suggested to exhibit the potency order of Ap(CH2)pp > App(CH2)p > ATP > 2-methylthio ATP (2MeSATP) and P2Y-purinergic receptors were suggested to exhibit the potency order of 2MeSATP ≫ ATP > Ap(CH2)pp = App(CH2)p. Whether these two putative receptor subtypes account for all of the effects of ADP and ATP is an open question. Indeed, data obtained with several cultured cell lines suggest a third subtype of receptor of the P2-purinergic receptor class (Dubyak and De Young, 1985).