Stresscopins and their uses

Abstract

The invention provides novel nucleic acids and polypeptides, referred to herein as stresscopin 1 and stresscopin 2, which preferentially activate the CRH-R2 receptor over the R1 receptor. Stresscopins, analogs and mimetics, and related CRH-R2 agonists suppress food intake and heat-induced edema; but do not induce substantial release of ACTH. Stresscopin also finds use in the recovery phase of stress responses, as an anti-inflammatory agent, as a hypotensive agent, as a cardioprotective agent, and in the treatment of psychiatric and anxiolytic disorders. Stresscopin nucleic acid compositions find use in identifying homologous or related proteins and the DNA sequences encoding such proteins; in producing compositions that modulate the expression or function of the protein; and in studying associated physiological pathways.

1 . A composition comprising a stresscopin peptide, wherein said stresscopin peptide comprises at least 18 contiguous amino acids of the sequence set forth in any one of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5 or SEQ ID NO:6.  
     
     
         2 . A composition according to  claim 1 , wherein said peptide comprises at least 30 contiguous amino acids of the sequence set forth in any one of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5 or SEQ ID NO:6.  
     
     
         3 . The composition according to  claim 1 , wherein said composition further comprises a pharmaceutically acceptable carrier.  
     
     
         4 . A method of appetite suppression, the method comprising administering to an individual the composition of  claim 3 .  
     
     
         5 . A method for cardioprotection, the method comprising administering to an individual the composition of  claim 3 .  
     
     
         6 . A method for reduction of edema, the method comprising comprising administering to an individual the composition of  claim 3 .  
     
     
         7 . A method for reduction of inflammation, and organ graft rejection the method comprising administering to an individual the composition of  claim 3 .  
     
     
         8 . A method for the reduction of hypertension, the method comprising administering to an individual the composition of  claim 3 .  
     
     
         9 . A method for the treatment of stress related to trauma, the method comprising administering to an individual the composition of  claim 3 .  
     
     
         10 . A method of treatment for affective disorders, the method comprising comprising administering to an individual the composition of  claim 3 .  
     
     
         11 . An isolated nucleic acid molecule comprising a cDNA sequence encoding a mammalian stresscopin protein that will hybridize under stringent conditions of 50° C. or higher in the presence of 0.1×SSC to the sequence set forth in any one of SEQ ID NO:1 or SEQ ID NO:4, or encodes the peptide in any one of SEQ ID NO:3 or SEQ ID NO:6.  
     
     
         12 . An isolated nucleic acid according to  claim 11 , wherein said cDNA sequence is of human origin.  
     
     
         13 . An isolated nucleic acid molecule according to  claim 12 , wherein said human stresscopin protein comprises the sequence set forth in any one of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5 or SEQ ID NO:6.  
     
     
         14 . An isolated nucleic acid molecule according to  claim 13 , wherein said nucleic acid comprises the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:4.  
     
     
         15 . The nucleic acid of  claim 11 , further comprising a vector sequence.  
     
     
         16 . The nucleic acid of  claim 15 , wherein said vector comprises a transcription cassette operably linked to said stresscopin cDNA sequence.  
     
     
         17 . The nucleic acid of  claim 15 , wherein said vector is a plasmid.  
     
     
         18 . The nucleic acid of  claim 15 , wherein said vector is a retrovirus.  
     
     
         19 . The nucleic acid of  claim 1   5 , wherein said vector is an adenovirus.  
     
     
         20 . An antibody that specifically recognizes a stresscopin peptide.  
     
     
         21 . A non-human transgenic animal model for stresscopin gene function wherein said transgenic animal comprises an introduced alteration in a stresscopin gene.  
     
     
         22 . A method of screening for biologically active agents that modulate stresscopin function, the method comprising: combining a candidate biologically active agent with any one of:(a) a mammalian stresscopin peptide;(b) a cell comprising a nucleic acid encoding a mammalian stresscopin peptide; or(c) a non-human transgenic animal model for stresscopin gene function comprising one of:(i) a knockout of an stresscopin gene; (ii) an exogenous and stably transmitted mammalian stresscopin gene sequence; and determining the effect of said agent on stresscopin function.