Novel G Protein-Coupled Receptor

Abstract

The present invention is directed to novel G protein-coupled receptors that are found predominantly in the dorsal root ganglia. The invention encompasses both the receptor proteins as well as nucleic acids encoding the proteins. In addition, the present invention is directed to methods and compositions which utilize the receptors.

1 - 42 . (canceled) 
     
     
         43 . A substantially pure protein, wherein the protein comprises the amino acid sequence SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, or SEQ ID NO:13. 
     
     
         44 . A substantially pure polynucleotide encoding a protein of  claim 43 . 
     
     
         45 . The polynucleotide of  claim 44  wherein the polynucleotide comprises the nucleotide sequence SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, or SEQ ID NO:14. 
     
     
         46 . A vector comprising the polynucleotide of  claim 44 . 
     
     
         47 . A host cell transformed with a vector of  claim 46 . 
     
     
         48 . A recombinant protein produced by the host cell of  claim 47 . 
     
     
         49 . A method for assaying a test compound for its ability to inhibit the binding of a ligand to human dorsal root receptor-2 (hDRR-2), human dorsal root receptor-3 (hDRR-3), human dorsal root receptor-4 (hDRR-4), human dorsal root receptor-5 (hDRR-5), or human dorsal root receptor-6 (hDRR-6) comprising:
 a) incubating a source containing hDRR-2 according to SEQ ID NO:5, hDRR-3 according to SEQ ID NO:7, hDRR-4 according to SEQ ID NO:9, hDRR-5 according to SEQ ID NO:11, or hDRR-6 according to SEQ ID NO:13, but substantially free of other G protein coupled receptors, with:
 i) a ligand known to bind to hDRR-2 according to SEQ ID NO:5, hDRR-3 according to SEQ ID NO:7, hDRR-4 according to SEQ ID NO:9, hDRR-5 according to SEQ ID NO:11, or hDRR-6 according to SEQ ID NO:13; and 
 ii) the test compound; and 
   b) determining the extent to which the ligand binding is displaced by the test compound.   
     
     
         50 . A method for determining if a test compound is an agonist of human DRR-2, human DRR-3, human DRR-4, human DRR-5, or human DRR-6, comprising:
 a) determining the ability of the test compound to bind to human DRR-2, human DRR-3, human DRR-4, human DRR-5, or human DRR-6; and   b) determining whether the test compound causes a statistically significant increase in either intracellular adenyl cyclase activity or the intracellular concentration of calcium.   
     
     
         51 . A method for determining if a test compound is an antagonist of human DRR-2, human DRR-3, human DRR-4, human DRR-5, or human DRR-6, comprising:
 a) incorporating a DNA molecule encoding human DRR-2, human DRR-3, human DRR-4, human DRR-5, or human DRR-6, into an expression vector so that it is operably linked to a promoter;   b) transfecting the expression vector into a host cell;   c) selecting cells transfected in step b) that have constitutively activated DRR-1 receptors as evidenced by either:
 i) a statistically significant increase in intracellular adenyl cyclase activity; or 
 ii) a statistically significant increase in intracellular calcium concentration; 
   d) determining the binding of the test compound to the cells selected in step c); and   e) determining if the test compound causes a statistically significant decrease in either the adenyl cyclase activity or the calcium concentration relative to control cells not contacted with the test compound.