Methods of modifying feeding behavior, compounds useful in such methods, and DNA encoding a hypothalamic atypical neuropeptide Y/peptide YY receptor (Y5)

Abstract

This invention provides methods of modifying feeding behavior, including increasing or decreasing food consumption, e.g., in connection with treating obesity, bulimia or anorexia. These methods involve administration of compounds are selective agonists or antagonists or the Y5 receptor. One such compound has the structure: In addition, this invention provides an isolated nucleic acid molecule encoding a Y5 receptor, an isolated Y5 receptor protein, vectors comprising an isolated nucleic acid molecule encoding a Y5 receptor, cells comprising such vectors, antibodies directed to the Y5 receptor, nucleic acid probes useful for detecting nucleic acid encoding Y5 receptors, antisense oligonucleotides complementary to any unique sequences of a nucleic acid molecule which encodes a Y5 receptor, and nonhuman transgenic animals which express DNA a normal or a mutant Y5 receptor.

1 - 42 . (canceled)  
     
     
         43 . An isolated nucleic acid encoding a Y5 receptor.  
     
     
         44 - 59 . (canceled)  
     
     
         60 . A purified Y5 receptor protein.  
     
     
         61 - 92 . (canceled)  
     
     
         93 . A nucleic acid probe comprising a nucleic acid of at least 15 nucleotides capable of specifically hybridizing with a unique sequence included within the sequence of a nucleic acid encoding a Y5 receptor of  claim 43 .  
     
     
         94 . A nucleic acid probe of  claim 93 , wherein the nucleic acid is DNA.  
     
     
         95 . A nucleic acid probe of  claim 93 , wherein the nucleic acid is RNA.  
     
     
         96 - 98 . (canceled)  
     
     
         99 . An antibody capable of binding to a Y5 receptor of  claim 43 .  
     
     
         100 . An antibody of  claim 99 , wherein the Y5 receptor is a human Y5 receptor.  
     
     
         101 . An antibody capable of competitively inhibiting the binding of the antibody of  claim 99  to a Y5 receptor.  
     
     
         102 . An antibody of  claim 99  wherein the antibody is a monoclonal antibody.  
     
     
         103 . A monoclonal antibody of  claim 102  directed to an epitope of a Y5 receptor present on the surface of a Y5 receptor expressing cell.  
     
     
         104 - 108 . (canceled)  
     
     
         109 . A pharmaceutical composition which comprises an amount of the antibody of  claim 99  effective to block binding of a ligand to the Y5 receptor and a pharmaceutically acceptable carrier.  
     
     
         110 - 147 . (canceled)  
     
     
         148 . A method of screening a plurality of chemical compounds not known to inhibit the activation of a Y5 receptor to identify a compound which inhibits the activation of the Y5 receptor, which comprises 
 (a) contacting a cell transfected with and expressing the Y5 receptor with the plurality of compounds in the presence of a known Y5 receptor agonist, under conditions permitting activation of the Y5 receptor;    (b) determining whether the activation of the Y5 receptor is reduced in the presence of the plurality of compounds, relative to the activation of the Y5 receptor in the absence of the plurality of compounds; and if so    (c) separately determining the inhibition of activation of the Y5 receptor for each compound included in the plurality of compounds, so as to thereby identify the compound which inhibits the activation of the Y5 receptor.    
     
     
         149 - 160 . (canceled)  
     
     
         161 . A method of detecting the presence of a human Y5 receptor on the surface of a cell which comprises contacting the cell with the antibody of  claim 99  under conditions permitting binding of the antibody to the receptor, detecting the presence of the antibody bound to the cell, and thereby detecting the presence of a human Y5 receptor on the surface of the cell.  
     
     
         162 - 173 . (canceled)  
     
     
         174 . A method of preparing the purified Y5 receptor of  claim 60  which comprises: 
 (a) inducing cells to express Y5 receptor;    (b) recovering the receptor from the induced cells; and    (c) purifying the receptor so recovered.    
     
     
         175 . A method of preparing the purified Y5 receptor of  claim 60  which comprises: 
 (a) inserting nucleic acid encoding Y5 receptor in a suitable vector;    (b) introducing the resulting vector in a suitable host cell;    (c) placing the resulting cell in suitable condition permitting the production of the isolated Y5 receptor;    (d) recovering the receptor produced by the resulting cell; and    (e) purifying the receptor so recovered.