Variants of corticotropin releasing hormone receptor type 1 and uses thereof

Abstract

The present invention identifies four new isoforms of human corticotropin releasing hormone receptor type 1 (CRH-R1e, 1f, 1g and 1h) and three new isoforms of mouse corticotropin releasing hormone receptor type 1 (mCRH-R1c, 1e and 1f). The data indicate that polymorphism of CRH-R1 expression is related to anatomic location, skin physiological or pathologic status, specific cell type, external stress (UV), and that cAMP dependent pathways and TPA may regulate CRH-R1.

1 . DNA encoding a corticotropin releasing hormone receptor type 1 protein comprising an amino acid sequence selected from the group consisting of SEQ ID No. 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 31, 32, 33, 34, 35, 36, and 37.  
     
     
         2 . A vector capable of expressing the DNA of  claim 1 , wherein said vector comprises said DNA and regulatory elements necessary for expression of said DNA in a cell.  
     
     
         3 . The vector of  claim 2 , wherein said DNA encodes a corticotropin releasing hormone receptor type 1 protein comprising an amino acid sequence selected from the group consisting of SEQ ID No. 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 31, 32, 33, 34, 35, 36, and 37.  
     
     
         4 . A host cell transfected with the vector of  claim 2 , wherein said vector expresses a corticotropin releasing hormone receptor type 1 protein.  
     
     
         5 . The host cell of  claim 4 , wherein said cell is selected from the group consisting of bacterial cells, mammalian cells, plant cells and insect cells.  
     
     
         6 . The host cell of  claim 5 , wherein said bacterial cell is  E. coli.    
     
     
         7 . An isolated corticotropin releasing hormone receptor type 1 protein encoded by the DNA of  claim 1  and comprising an amino acid sequence selected from the group consisting of SEQ ID No. 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 31, 32, 33, 34, 35, 36, and 37.  
     
     
         8 . An antibody directed against the corticotropin releasing receptor type 1 protein of  claim 7 .  
     
     
         9 . The antibody of  claim 8 , wherein said antibody is a monoclonal antibody.  
     
     
         10 . A pharmaceutical composition comprising the corticotropin releasing hormone receptor type 1 protein of  claim 7  and a pharmaceutically acceptable carrier.  
     
     
         11 . A method of treating a pathophysiological state, comprising the step of administering the pharmaceutical composition of  claim 10  to an individual in need of such treatment.  
     
     
         12 . The method of  claim 11 , wherein said pathophysiological state is selected from the group consisting of hyperproliferative epidermal disorder, allergic contact dermatitis, autoimmune disorder, epidermal carcinogenesis, and malignant transformation of epidermal or dermal melanocytes.  
     
     
         13 . The DNA of  claim 1 , wherein said sequence differs in codon sequence due to the degeneracy of the genetic code, and wherein said sequence encodes a corticotropin releasing hormone receptor type 1 protein.  
     
     
         14 . A vector capable of expressing the DNA of  claim 13 , wherein said vector comprises said DNA and regulatory elements necessary for expression of said DNA in a cell.  
     
     
         15 . A host cell transfected with the vector of  claim 14 , wherein said vector expresses a corticotropin releasing hormone receptor type 1 protein.  
     
     
         16 . The host cell of  claim 15 , wherein said cell is selected from the group consisting of bacterial cells, mammalian cells, plant cells and insect cells.  
     
     
         17 . The host cell of  claim 15 , wherein said bacterial cell is  E. coli.    
     
     
         18 . A method of protecting skin cells against damage induced by an environmental factor, comprising the step of: 
 inducing the expression of corticotropin releasing hormone receptor type 1g in said skin cells, wherein the expression of said receptor type 1g protects said skin cells against said damage.    
     
     
         19 . The method of  claim 18 , wherein said damage is induced by solar radiation.  
     
     
         20 . The method of  claim 18 , wherein inducing the expression of corticotropin releasing hormone receptor type 1g in said skin cells inhibits proliferation in said cells.  
     
     
         21 . The method of  claim 18 , wherein inducing the expression of corticotropin releasing hormone receptor type 1g in said skin cells regulates production of cAMP in said skin cells.  
     
     
         22 . A method of screening for a compound that induces the expression of corticotropin releasing hormone receptor type 1f or 1g, comprising the steps of: 
 contacting said compound with skin cells; and    determining the expression of said receptor type 1f or 1g in cells that are or are not treated with said compound, wherein increased expression of said receptor type 1f or 1g in treated cells compared to untreated cells indicates said compound induces expression of said receptor type 1f or 1g.    
     
     
         23 . The method of  claim 22 , wherein said compound comprises a treatment for a pathophysiological state.  
     
     
         24 . The method of  claim 23 , wherein said pathophysiological state is selected from the group consisting of hyperproliferative epidermal disorder and neuroendocrine disorder.  
     
     
         25 . A method of regulating an extracellular concentration of corticotropin releasing hormone or corticotropin releasing hormone related peptides, comprising the step of: 
 administering corticotropin releasing hormone receptor type 1e or 1h to an individual, wherein said receptor type 1e or 1h regulates said extracellular concentration of corticotropin releasing hormone or corticotropin releasing hormone related peptides by binding and slowly releasing said hormone or said peptides in said individual.    
     
     
         26 . The method of  claim 25 , wherein administering said receptor type 1e or 1h comprises a treatment for a pathophysiological state.  
     
     
         27 . The method of  claim 25 , wherein said pathophysiological state comprises an inflammatory skin disease.  
     
     
         28 . The method of  claim 27 , wherein said skin disease is selected from the group consisting of psoriasis, allergic contact dermatitis, and abnormal hair growth.  
     
     
         29 . The method of  claim 25 , wherein administering said receptor type 1e or 1h to the individual comprises injecting said receptor type 1e or 1h intravenously.  
     
     
         30 . The method of  claim 25 , wherein administering said receptor type 1e or 1h to the individual inhibits production of cAMP in said individual.  
     
     
         31 . The method of  claim 25 , wherein said receptor type 1e or 1h comprises a complex between said receptor type 1e or 1h and said corticotropin releasing hormone or said corticotropin releasing hormone related peptides.  
     
     
         32 . The method of  claim 31 , wherein said complex is administered to said individual by intravenous or intratissue injection.