Methods for modulating gastric secretion using prokineticin receptor antagonists

Abstract

The invention provides methods of modulating gastric acid secretion by administering an amount of a prokineticin receptor antagonist effective to alter one or more indicia of gastric acid secretion, wherein the antagonist contains an amino acid sequence at least 80% identical to amino acids to 7 to 77 of SEQ ID NO:3, which includes (a) the 10 conserved cysteine residues of SEQ ID NO:3, and (b) from 0 to 9 of amino acids 78 to 86 of SEQ ID NO:3, wherein amino acids 1 to 6 of the antagonist do not consist of amino acids AVITGA (SEQ ID NO:21). In another embodiment, the antagonist contains an amino acid sequence at least 80% identical to amino acids to 7 to 77 of SEQ ID NO:6, which includes (a) the 10 conserved cysteine residues of SEQ ID NO:6, and (b) from 0 to 4 of amino acids 78 to 81 of SEQ ID NO:6, wherein amino acids 1 to 6 of the antagonist do not consist of amino acids AVITGA (SEQ ID NO:21).

1 - 41 . (canceled)  
     
     
         42 . A method for screening for a compound for modulating gastric acid or pepsinogen secretion in a mammal, comprising: 
 (a) contacting a receptor selected from the group consisting of PK2 receptor and PK1 receptor with a compound under conditions wherein the PK2 receptor and PK1 receptor promote a predetermined signal and the compound modulates the predetermined signal; and    (b) determining the ability of the compound to modulate the predetermined signal, wherein the predetermined signal is one or more indicia of gastric acid or pepsinogen secretion, wherein the compound is identified as a compound for modulating gastric acid or pepsinogen secretion in a mammal.    
     
     
         43 . The method of  claim 42 , wherein the provided PK receptor antagonist is identified by contacting a receptor selected from the group consisting of PK2 receptor and PK1 receptor with one or more candidate compounds under conditions wherein PK promotes a predetermined signal and identifying a compound that reduces said predetermined signal.  
     
     
         44 . (canceled)  
     
     
         45 . The method of  claim 42 , wherein said predetermined signal is calcium ion mobilization.  
     
     
         46 . (canceled)  
     
     
         47 . The method of  claim 42 , wherein said receptor is a mouse PK2 receptor.  
     
     
         48 . The method of  claim 43 , wherein said receptor is a mouse PK2 receptor.  
     
     
         49 . The method of  claim 45 , wherein the provided PK2 receptor antagonist is identified by contacting a receptor selected from the group consisting of PK2 receptor and PK1 receptor with one or more candidate compounds in the presence of a receptor agonist under conditions wherein said agonist binds to the selected receptor and identifying a compound that reduces said binding.  
     
     
         50 . (canceled)  
     
     
         51 . The method of  claim 49 , wherein said receptor agonist is PK2.  
     
     
         52 . The method of  claim 49 , wherein said PK2 is human PK2.  
     
     
         53 - 57 . (canceled)