Human endothelin-bombesin receptor

Abstract

A human endothelin-bombesin receptor polypeptide and DNA (RNA) encoding such polypeptide and a procedure for producing such polypeptide by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptide for identifying agonists and antagonists to such polypeptide. Agonists to the endothelin-bombesin receptor polypeptide of the present invention may be used to treat asthma, Parkinson's Disease, acute heart failure, hypotension and osteoporosis. Antagonists against such polypeptides may be used therapeutically to treat hypertension, ulcerigenesis, subarachnoid hemorrhage, asthma, tumors, ciclosporin toxicity, cancer and septic shock. Also disclosed are diagnostic methods for detecting mutations in the polynucleotides of the present invention and for detecting levels of the soluble polypeptides in samples derived from a host.

What is claimed is:  
     
         1 . An isolated polynucleotide comprising a member selected from the group consisting of: 
 (a) a polynucleotide encoding the polypeptide comprising amino acid-27 to 613 as set forth in SEQ ID NO: 2 ;    (b) a polynucleotide encoding the polypeptide comprising amino acid 1 to 613 as set forth in SEQ ID NO: 2 ;    (c) a polynucleotide capable of hybridizing to and which is at least 70% identical to the polynucleotide of (a) or (b); and    (d) a polynucleotide fragment of the polynucleotide of (a), (b) or (c).    
     
     
         2 . The polynucleotide of  claim 1  wherein the polynucleotide is DNA.  
     
     
         3 . An isolated polynucleotide comprising a member selected from the group consisting of: 
 (a) a polynucleotide encoding a mature polypeptide encoded by the DNA contained in ATCC Deposit No. 75823;    (b) a polynucleotide encoding a polypeptide expressed by the DNA contained in ATCC Deposit No. 75823;    (c) a polynucleotide capable of hybridizing to and which is at least 70% identical to the polynucleotide of (a) or (b); and    (d) a polynucleotide fragment of the polynucleotide of (a), (b) or (c).    
     
     
         4 . A vector containing the DNA of  claim 2 .  
     
     
         5 . A host cell transformed or transfected with the vector of  claim 4 .  
     
     
         6 . A process for producing a polypeptide comprising: expressing from the host cell of  claim 5  the polypeptide encoded by said DNA.  
     
     
         7 . A process for producing cells capable of expressing a polypeptide comprising transforming or transfecting the cells with the vector of  claim 4 .  
     
     
         8 . A receptor polypeptide comprising a member selected from the group consisting of: 
 (a) a polypeptide having the deduced amino acid sequence of SEQ ID NO: 2  and fragments, analogs and derivatives thereof; and    (b) a polypeptide encoded by the cDNA of ATCC Deposit No. 75823 and fragments, analogs and derivatives of said polypeptide.    
     
     
         9 . An antibody against the polypeptide of  claim 8 .  
     
     
         10 . A compound which activates the polypeptide of  claim 8 .  
     
     
         11 . A compound which inhibits activation the polypeptide of  claim 8 .  
     
     
         12 . A method for the treatment of a patient having need to activate an ETBR receptor comprising administering to the patient a therapeutically effective amount of the compound of  claim 10 .  
     
     
         13 . A method for the treatment of a patient having need to inhibit an ETBR receptor comprising administering to the patient a therapeutically effective amount of the compound of  claim 11 .  
     
     
         14 . The method of  claim 12  wherein said compound is a polypeptide and a therapeutically effective amount of the compound is administered by providing to the patient DNA encoding said agonist and expressing said agonist in vivo.  
     
     
         15 . The method of  claim 13  wherein said compound is a polypeptide and a therapeutically effective amount of the compound is administered by providing to the patient DNA encoding said antagonist and expressing said antagonist in vivo.  
     
     
         16 . A method for identifying compounds which bind to and activate the receptor polypeptide of  claim 8  comprising: 
 (a) contacting a cell expressing on the surface thereof the receptor polypeptide, said receptor being associated with a second component capable of providing a detectable signal in response to the binding of a compound to said receptor polypeptide, with a compound under conditions sufficient to permit binding of the compound to the receptor polypeptide; and  
 (b) identifying if the compound is capable of receptor binding by detecting the signal produced by said second component.  
 
     
     
         17 . A method for identifying compounds which bind to and inhibit activation of the polypeptide of  claim 8  comprising: 
 (a) contacting a cell expressing on the surface thereof the receptor polypeptide, said receptor being associated with a second component capable of providing a detectable signal in response to the binding of a compound to said receptor polypeptide, with an analytically detectable ligand known to bind to the receptor polypeptide and a compound to be screened under conditions to permit binding to the receptor polypeptide; and  
 (b) determining whether the compound inhibits activation of the polypeptide by detecting the absence of a signal generated from the interaction of the ligand with the polypeptide.  
 
     
     
         18 . A process for diagnosing a disease or a susceptibility to a disease related to an under-expression of the polypeptide of  claim 8  comprising determining a mutation in the nucleic acid sequence encoding said polypeptide.  
     
     
         19 . The polypeptide of  claim 8  wherein the polypeptide is a soluble fragment of the polypeptide and is capable of binding a ligand for the receptor.  
     
     
         20 . A diagnostic process comprising analyzing for the presence of the polypeptide of  claim 19  in a sample derived from a host.