The Cloning and Expression of G Protein-Coupled P2Y Nucleotide Receptors

Abstract

The existence of cell surface receptors for extracellular adenine nucleotides in mammalian cells has been postulated for decades (Burn-stock, 1972), based on scores of reports on diverse responses to these molecules in a wide variety of tissues and cell types (Dubyak and El-Moatassim, 1993). Pharmacological studies have provided evidence for the expression of two major types of nucleotide receptors: those belonging to the G protein-coupled receptor family and those belonging to the ligand-gated ion channel family. Nucleotide receptors (P2 purinergic receptors) are distinct from P1 receptors for adenosine, and, from results of earlier studies, were thought to be selective for purine nucleotides, in particular adenosine 5′-triphosphate (ATP), adenosine 5′-diphosphate (ADP) and various analogs, including 2MeSATP, α,β-MeATP, and β,γ-MeATP. Recent studies have demonstrated that uridine nucleotides are equally or more effective than adenine nucleotides in activating several G protein-coupled P2 receptor subtypes, raising a question as to the appropriateness of referring to this family of receptors as “purinergic.” Nonetheless, nucleotide receptors have retained the designation “P2,” which now refers to both their purine- and/or pyrimidine-based nucleotide agonists.