The diverse series of recombinant P2Y purinoceptors

A cDNA encoding a P2Y purinoceptor was originally cloned from chick brain and the bovine and human homologues have recently been obtained. These are seven-transmembrane-domain polypetides, i.e. G protein-coupled receptors. When activated by agonists, this P2Y receptor mobilizes intracellular Ca2+ and has been shown to be coupled to inositol-1,4,5-trisphosphate formation. Its pharmacology has been established in several expression systems, using both ligand binding and functional responses: 2-methylthioATP has the highest potency of nucleotides and derivatives tested, while UTP and alpha, beta-methylene ATP are inactive. This was hence assigned as a new subtype of the pharmacologically defined P2Y receptors, P2Y1. P2Y1 receptors are exceptionally abundant in the brain. A P2U receptor reported by others can be designated P2Y2. Another P2 receptor subtype, P2Y3, now cloned as a cDNA from the brain and expressed in oocytes and in transfected cells, shows a quite different ligand potency profile to the first two. A fourth subtype is expressed primarily in certain haemopoietic cells and in cardiac muscle. A putative fifth subtype is expressed only in T lymphocytes, upon activation. Yet other P2Y subtypes are indicated by recent cloning studies. The amino acid sequences of all of these P2 receptors, while displaying some homology, are strikingly diverse: they form a separate and unusual new family in the G protein-coupled receptor main superfamily.