P2Y Receptors: Structure and Function

Abstract

Following the finding that nucleotides act as extracellular signalling molecules by interaction with cell surface transmembrane P2 receptors, it has now been recognised that this mode of regulation is widespread, exerting a ubiquitous influence on physiological function. Indeed, P2 receptors are present on most cells in the body (Ralevic and Burnstock 1998) P2 receptor regulation via disparate cell types is mirrored by the diversity of cellular responses that these receptors elicit on activation by endogenous nucleotides. This diversity in turn comes, in part from multiple P2 receptors, and in part from different responses to activation of the same receptors in different cell types. P2 receptors are subdivided into P2X receptors with intrinsic ion channels and G protein-coupled P2Y receptors (Abbracchio and Burnstock 1994; Fredholm et al. 1997). The wide spread distribution of multiple P2Y receptor subtypes represents an important challenge in characterising and classifying this subfamily of receptors in order to understand the manner in which their activation by native extracellular nucleotides gives rise to cognate cellular responses. It has been evident for some time that different P2Y receptor-subtypes can give rise to distinct cellular responses, even when two subtypes are located on the same cell, and even when both are coupled to a similar level of stimulation of phospholipase C. In this chapter, the relationships between the molecular and pharmacological properties of these P2Y receptors is discussed, as well as the contribution of structural diversity to the control of intracellular signalling pathways to understand at the cellular level how the different receptors of the P2Y subfamily generate appropriate functional responses. To pursue this objective, an overview of some current issues concerning the P2Y receptors is provided.