Use of purinergic receptor modulators and related reagents

Abstract

The invention provides a method of treatment for an animal having a disease state associated with a genitourinary disorder with a purinergic receptor modulator. Also provided, is a transgenic animal having a disrupted purinergic receptor gene. The invention further provides for a method of screening using the transgenic animal as a positive control.

What is claimed is:  
     
         1 . A method of treating a subject having a disease state associated with a genitourinary or pain disorder comprising administering to the animal an effective amount of a purinoreceptor modulator.  
     
     
         2 . The method of  claim 1 , wherein the genitourinary disorder is an overactive bladder.  
     
     
         3 . The method of  claim 1 , wherein the genitourinary disorder is outlet obstruction.  
     
     
         4 . The method of  claim 1 , wherein the genitourinary disorder is outlet insufficiency.  
     
     
         5 . The method of  claim 1 , wherein the genitourinary disorder is pelvic hypersensitivity.  
     
     
         6 . The method of  claim 1 , wherein the pain disorder is peripheral pain, inflammatory pain, or tissue injury pain.  
     
     
         7 . The method of  claim 1 , wherein the purinoreceptor modulator is a P2X receptor complex modulator.  
     
     
         8 . The method of  claim 7 , wherein the P2X receptor complex comprises at least one P2X 3  receptor subunit.  
     
     
         9 . The method of  claim 7 , wherein the P2X receptor complex modulator is an antagonist.  
     
     
         10 . The method of  claim 7 , wherein the P2X receptor complex modulator is an agonist.  
     
     
         11 . The method of  claim 1 , wherein the subject is a mammal.  
     
     
         12 . The method of  claim 11 , wherein the mammal is a human.  
     
     
         13 . A transgenic animal containing an altered allele for the gene that naturally encodes and expresses a functional P2X 3  receptor subunit.  
     
     
         14 . The transgenic animal of  claim 13 , wherein the altered allele is a non-functional allele.  
     
     
         15 . The transgenic animal of  claim 13 , wherein the transgenic animal is a knockout (KO) animal.  
     
     
         16 . The KO animal of  claim 15 , wherein the phenotype of the KO animal relative to a wild-type control animal comprises: 
 a) an increase in urinary bladder capacity;    b) a lower frequency of urine voiding;    c) a larger voided volume; and    d) no significant change in cystometric pressure.    
     
     
         17 . The KO animal of  claim 15 , wherein the phenotype of the KO animal relative to a wild-type control animal comprises: 
 a) attenuated nociception in response to injection of ATP; or    b) attenuated nociception in response to injection of formalin.    
     
     
         18 . The KO animal of  claim 15 , wherein the animal is a mouse.  
     
     
         19 . A method for selecting a potential therapeutic.compound for use in the treatment of a disease state associated with a genitourinary disorder comprising: 
 a) administering the compound to a wild-type animal or an animal having a disease state associated with a genitourinary disorder;    b) measuring the resulting phenotype of wild-type animal or the animal having the disease state; and    c) comparing the resulting pheontype of the wild-type animal or the animal having the disease state to the phenotype of the knockout animal of  claim 16 .    
     
     
         20 . A method for selecting a potential therapeutic compound for use in the treatment of a disease state associated with a pain disorder comprising: 
 d) administering the compound to a wild-type animal or an animal having a disease state associated with a pain disorder;    e) measuring the resulting phenotype of wild-type animal or the animal having the disease state; and    f) comparing the resulting pheontype of the wild-type animal or the animal having the disease state to the phenotype of the knockout animal of  claim 17.