EXPRESSION CLONING OF AN ATP RECEPTOR FROM MOUSE NEUROBLASTOMA-CELLS

Extracellular ATP activates cell-surface metabotropic and ionotropic n ucleotide (P2) receptors in vascular, neural, connective, and immune t issues. These P2 receptors mediate a wealth of physiological processes , including nitric oxide-dependent vasodilation of vascular smooth mus cle and fast excitatory neurotransmission in sensory afferents. Althou gh ATP is now recognized as a signaling molecule, the cellular and mol ecular mechanisms underlying its actions have been difficult to study due to the absence of selective P2 receptor antagonists and cloned rec eptor genes. Nonetheless, five mammalian P2 receptor subtypes have bee n tentatively assigned based solely on agonist specificity and signali ng properties. Here we report the cloning of a mouse cDNA encoding a P 2 receptor that shares striking homology with several G protein-couple d peptide receptors. When expressed in Xenopus laevis oocytes, the clo ned receptor resembles a metabotropic P2U receptor; activation by eith er ATP or UTP elicits the mobilization of intracellular calcium. mRNA encoding the P2U purinergic receptor is found in neural and nonneural tissues.