Hemokinin-1 receptor and hemokinin-1-derived peptide

Abstract

The present invention provides a peptide having antagonist activity against SP, pain control activity, anti-inflammation activity, and anti-pruritic activity. The present invention further provides a method for searching for a therapeutic agent for pain, a therapeutic agent for inflammation, and a therapeutic agent for pruritus using G protein coupled receptor (GPR) 83, which is an HK-1 specific receptor.

1 . Use of GPR83 for screening a compound useful for treating pain, inflammation, or pruritus. 
     
     
         2 . The use according to  claim 1 , wherein GPR83 is:
 (i) a polypeptide consisting of the amino acid sequence represented by any one of SEQ ID NOS: 17 to 20;   (ii) a polypeptide containing a partial sequence of the amino acid sequence represented by any one of SEQ ID NOS: 17 to 20, and having HK-1 receptor activity;   (iii) a polypeptide comprising the amino acid sequence represented by any one of SEQ ID NOS: 17 to 20, and having HK-1 receptor activity;   (iv) a polypeptide consisting of an amino acid sequence that has a deletion, a substitution, and/or an addition of 1 to 10 amino acids with respect to the amino acid sequence of any one of the polypeptides (i) to (iii), and having HK-1 receptor activity; or   (v) a polypeptide comprising an amino acid sequence that has at least 90% sequence identity with the amino acid sequence of any one of the polypeptides (i) to (iii), and having HK-1 receptor activity.   
     
     
         3 . A method for screening a compound useful for treating pain, inflammation, or pruritus, comprising the steps of:
 bringing a compound assumed to be an antagonist against the function of an HK-1 receptor into contact with GPR83;   detecting the binding of the compound to and/or antagonist activity of the compound against GPR83; and   screening a compound useful for treating pain, inflammation, or pruritus.   
     
     
         4 . The method according to  claim 3 , comprising the steps of:
 preparing a cell membrane containing GPR83;   bringing a compound assumed to be an antagonist against the function of the HK-1 receptor into contact with the cell membrane; and   confirming whether the compound binds to GPR83 and thus exhibits antagonist activity.   
     
     
         5 . The method according to  claim 3 , wherein GPR83 is:
 (i) a polypeptide consisting of the amino acid sequence represented by any one of SEQ ID NOS: 17 to 20;   (ii) a polypeptide containing a partial sequence of the amino acid sequence represented by any one of SEQ ID NOS: 17 to 20, and having HK-1 receptor activity;   (iii) a polypeptide comprising the amino acid sequence represented by any one of SEQ ID NOS: 17 to 20, and having HK-1 receptor activity;   (iv) a polypeptide consisting of an amino acid sequence that has a deletion, a substitution, and/or an addition of 1 to 10 amino acids with respect to the amino acid sequence of any one of the polypeptides (i) to (iii), and having HK-1 receptor activity; or   (v) a polypeptide comprising an amino acid sequence that has at least 90% sequence identity with the amino acid sequence of any one of the polypeptides (i) to (iii), and having HK-1 receptor activity.   
     
     
         6 . A pharmaceutical composition for treating pain, inflammation, or pruritus, containing a GPR83 function inhibitor (selected from the group consisting of an antagonist, an antibody, antisense, and siRNA). 
     
     
         7 - 12 . (canceled)