Cloning of a novel G-protein coupled 7TM Receptor

Abstract

HNHCI32 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing HNHCI32 polypeptides and polynucleotides in the design of protocols for the treatment of infections such as bacterial, fungal, protozoan and viral infections, particularly infections caused by HIV-1 or HIV-2; pain; cancers; anorexia; bulimia; asthma; Parkinson's disease; acute heart failure; hypotension; hypertension; urinary retention; osteoporosis; angina pectoris; myocardial infarction; ulcers; asthma; allergies; benign prostatic hypertrophy; and psychotic and neurological disorders, including anxiety, schizophrenia, manic depression, delirium, dementia, severe mental retardation and dyskinesias, such as Huntington's disease or Gilles dela Tourett's syndrome, among others and diagnostic assays for such conditions.

What is claimed is:  
     
         1 . An isolated polynucleotide comprising a nucleotide sequence that has at least 80% identity to a nucleotide sequence encoding the polypetide of SEQ ID NO:2 or the corresponding fragment thereof; or a nucleotide sequence complementary to said nucleotide sequence.  
     
     
         2 . The polynucleotide of    claim 1    which is DNA or RNA.  
     
     
         3 . The polynucleotide of    claim 1    wherein said nucleotide sequence is at least 80% identical to that contained in SEQ ID NO:1.  
     
     
         4 . The polynucleotide of    claim 3    wherein said nucleotide sequence is contained in SEQ ID NO:1.  
     
     
         5 . The polynucleotide of    claim 1    wherein said encoding nucleotide sequence encodes the polypeptide of SEQ ID NO:2 or a fragment thereof.  
     
     
         6 . A polynucleotide probe or primer comprising at least 15 contiguous nucleotides of the polynucleotide of    claim 3   .  
     
     
         7 . A DNA or RNA molecule comprising an expression system wherein said expression system is capable of producing a HNHCI32 or a fragment thereof having at least 80% identity with a nucleotide sequence encoding the polypeptide of SEQ ID NO:2 or said fragment when said expression system is present in a compatible host cell.  
     
     
         8 . A host cell comprising the expression system of    claim 7   .  
     
     
         9 . A process for producing a HNHCI32 polypeptide or fragment comprising culturing a host of    claim 8    and under conditions sufficient for the production of said polypeptide or fragment.  
     
     
         10 . The process of    claim 9    wherein said polypeptide or fragment is expressed at the surface of said cell.  
     
     
         11 . Cells produced by the process of    claim 10   .  
     
     
         12 . The process of    claim 9    which further includes recovering the polypeptide or fragment from the culture.  
     
     
         13 . A process for producing a cell which produces a HNHCI32 polypeptide or a fragment thereof comprising transforming or transfecting a host cell with the expression system of    claim 7    such that the host cell, under appropriate culture conditions, produces a HNHCI32 polypeptide or fragment.  
     
     
         14 . A HNHCI32 polypeptide or a fragment thereof comprising an amino acid sequence which is at least 80% identical to the amino acid sequence contained in SEQ ID NO:2.  
     
     
         15 . The polypeptide of    claim 14    which comprises the amino acid sequence of SEQ ID NO:2, or a fragment thereof.  
     
     
         16 . A HNHCI32 polypeptide or fragment prepared by the method of    claim 12   .  
     
     
         17 . An antibody immunospecific for the HNHCI32 polypeptide of    claim 14   .  
     
     
         18 . A method for the treatment of a subject in need of enhanced HNHCI32 activity comprising: 
 (a) administering to the subject a therapeutically effective amount of an agonist to said receptor; and/or (b) providing to the subject HNHCI32 polynucleotide in a form so as to effect production of said receptor activity in vivo.    
     
     
         19 . A method for the treatment of a subject having need to inhibit HNHCI32 activity comprising: 
 (a) administering to the subject a therapeutically effective amount of an antagonist to said receptor; and/or    (b) administering to the subject a nucleic acid molecule that inhibits the expression of the nucleotide sequence encoding said receptor; and/or    (c) administering to the subject a therapeutically effective amount of a polypeptide that competes with said receptor for its ligand.    
     
     
         20 . A process for diagnosing a disease or a susceptibility to a disease in a subject related to expression or activity of HNHCI32 in a subject comprising: 
 (a) determining the presence or absence of a mutation in the nucleotide sequence encoding said HNHCI32 in the genome of said subject; and/or    (b) analyzing for the presence or amount of the HNHCI32 expression in a sample derived from said subject.    
     
     
         21 . A method for identifying compounds which bind to HNHCI32 comprising: 
 (a) contacting cells of    claim 11    with a candidate compound; and    (b) assessing the ability of said candidate compound to bind to said cells.    
     
     
         22 . The method of    claim 21    which further includes determining whether the candidate compound effects a signal generated by activation of the HNHCI32 polypeptide at the surface of the cell, wherein a candidate compound which effects production of said signal is identified as an agonist.  
     
     
         23 . An agonist identified by the method of    claim 22   .  
     
     
         24 . The method of    claim 21    which further includes contacting said cell with a known agonist for said HNHCI32; and 
 determining whether the signal generated by said agonist is diminished in the presence of said candidate compound, wherein a candidate compound which effects a diminution in said signal is identified as an antagonist for said HNHCI32.  
 
     
     
         25 . An antagonist identified by the method of    claim 24   .