CLONING, EXPRESSION, AND CHROMOSOMAL LOCALIZATION OF THE HUMAN URIDINE NUCLEOTIDE RECEPTOR GENE

Extracellular ATP and ADP mediate diverse physiological responses in m ammalian cells, in part through the activation of G protein-coupled P- 2 purinoceptors. The cloning and expression of cDNAs encoding several P-2 purinoceptor subtypes have enabled rapid advances in our understan ding of the structural and functional properties of these receptors. T he current report de scribes the isolation of a gene from a human geno mic library that encodes a protein with the greatest similarity to the human P-2U purinoceptor, a subtype that is distinguished by its abili ty to be activated by uridine nucleotides as well as adenine nucleotid es. When expressed in a mammalian cell line, this novel receptor is ac tivated specifically by UTP and UDP but not by ATP and ADP. Activation of this uridine nucleotide receptor resulted in increased inositol ph osphate formation and calcium mobilization. Fluorescence in situ hybri dization revealed that the gene encoding the uridine nucleotide recept or is located in region q13 of the X chromosome. Dendrogram analysis o f the G protein-coupled P-2 purinoceptors and the uridine nucleotide r eceptor indicates that these receptors belong to a family that may be more aptly named nucleotide receptors.