Methods of using transporter-like molecules to treat pain and pain-related disorders

Abstract

The invention relates to OCT-3 polypeptides, nucleic acid molecules encoding OCT-3, and uses thereof. OCT-3 is a protein that is expressed in the plasma membrane of biological cells, across which it regulates the transport of organic molecules.

What is claimed is:  
     
         1 . A method for identifying a compound capable of treating a pain disorder comprising assaying the ability of the compound to modulate the expression of an organic cation transporter 3 (OCT-3) nucleic acid, thereby identifying a compound capable of treating a pain disorder.  
     
     
         2 . The method of  claim 1 , wherein the oct-3 nucleic acid is selected from the group consisting of: 
 a) a nucleic acid molecule comprising the nucleotide sequence set forth in SEQ ID NO:1, 3, or 5; and    b) a nucleic acid molecule comprising a nucleotide sequence which is at least 80 percent identical to the nucleotide sequence of SEQ ID NO: 1, 3, or 5.    
     
     
         3 . A method for identifying a compound capable of treating a pain disorder comprising assaying the ability of the compound to modulate the activity of an organic cation transporter 3 (OCT-3) polypeptide, thereby identifying a compound capable of treating a pain disorder.  
     
     
         4 . The method of  claim 3 , wherein the OCT-3 polypeptide is selected from the group consisting of: 
 a) a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2,4, or 6; and    b) a polypeptide comprising a polypeptide sequence which is at least 70 percent identical to the polypeptide sequence of SEQ ID NO:2, 4, or 6.    
     
     
         5 . A method for identifying a compound capable of modulating an organic cation transporter 3 (OCT-3) activity, comprising: 
 (a) contacting a cell which expresses OCT-3 with a test compound; and    (b) assaying the ability of the test compound to modulate the expression of an OCT-3 nucleic acid or the activity of an OCT-3 polypeptide, thereby identifying a compound capable of modulating an OCT-3 activity.    
     
     
         6 . A method for identifying a compound capable of modulating an organic cation transporter 3 (OCT-3) activity, comprising: 
 (a) contacting a polypeptide comprising the amino acid sequence of SEQ ID NO:2, 4, or 6 with a test compound; and    (b) assaying the ability of the test compound to modulate an activity of the polypeptide, thereby identifying a compound capable of modulating an OCT-3 activity.    
     
     
         7 . A method for modulating an OCT-3 activity comprising contacting an OCT-3 polypeptide or a cell expressing an OCT-3 polypeptide with a compound which binds to the polypeptide in a sufficient concentration to modulate the OCT-3 activity.  
     
     
         8 . The method of  claim 7 , wherein the OCT-3 polypeptide comprises an amino acid sequence which is at least 80 percent identical to the amino acid sequence of SEQ ID NO:2, 4, or 6, wherein said percent identity is calculated using the ALIGN program for comparing amino acid sequences, a PAM120 weight residue table, a gap length penalty of 12, and a gap penalty of 4.  
     
     
         9 . The method of any of claims  1 ,  3 ,  5 ,  6  and  7 , wherein the compound or modulator is a small molecule.  
     
     
         10 . The method of any of claims  1 ,  3 ,  5 ,  6  and  7 , wherein the compound or modulator is an anti OCT-3 antibody.  
     
     
         11 . The method of any of claims  1 ,  3 ,  5 ,  6  and  7 , wherein the compound or modulator is an OCT-3 ribozyme.  
     
     
         12 . A method for treating a subject having a pain disorder characterized by aberrant OCT-3 polypeptide activity or aberrant OCT-3 nucleic acid expression, comprising administering to the subject an OCT-3 modulator, thereby treating the subject having a pain disorder.  
     
     
         13 . The method of  claim 9 , wherein the modulator is selected from the group consisting of a small molecule OCT-3 agonist, a small molecule OCT-3 antagonist, an anti-OCT-3 antibody, an antisense oct-3 molecule, and an oct-3 ribozyme.  
     
     
         14 . A pharmaceutical formulation for the treatment of a pain disorder, comprising a compound that activates an organic cation transporter 3 (OCT-3) polypeptide activity or an OCT-3 nucleic acid expression, mixed with a pharmaceutically acceptable carrier.  
     
     
         15 . The pharmaceutical formulation of  claim 14 , wherein the compound is selected from the group consisting of a small molecule OCT-3 agonist, a small molecule OCT-3 antagonist, an anti-OCT-3 antibody, an antisense oct-3 molecule, and an oct-3 ribozyme.  
     
     
         16 . A genetically engineered nonhuman mammal in which the expression of an oct-3 gene has been inactivated.  
     
     
         17 . A transgenic animal which expresses a human oct-3 gene.