Orphan opioid receptor and recombinant materials for its production

Abstract

Genes encoding opioid receptors (including opioid-like receptor (ORL) proteins) can be retrieved from vertebrate libraries using the murine probe disclosed herein under low-stringency conditions. The DNA sequence shown in FIG. 5 or its complement can be used to obtain the human delta, kappa and mu genes as well as the murine mu gene and human ORL-1. The probe provided encodes the murine delta opioid receptor.

1 . An isolated and purified or recombinant DNA molecule containing a nucleotide sequence encoding an opioid receptor which hybridizes under conditions of low stringency to a probe consisting of the nucleotide sequence shown in FIG. 5 or to its complement.  
     
     
         2 . The DNA molecule of  claim 1  wherein said nucleotide sequence encodes human delta opioid receptor, human kappa opioid receptor, human mu opioid receptor, murine delta opioid receptor, murine mu opioid receptor or ORL-1.  
     
     
         3 . A DNA molecule comprising an expression system capable, when transformed into a host, of producing an opioid receptor in the host, which expression system comprises a nucleotide sequence encoding said opioid receptor operably linked to heterologous control sequences operable in said host, wherein said opioid receptor is defined as encoded by a nucleotide sequence which hybridizes under conditions of low stringency to the nucleotide sequence of FIG. 5 or to its complement.  
     
     
         4 . The DNA molecule of  claim 3  wherein said opioid receptor is a human delta opioid receptor, human kappa opioid receptor, human mu opioid receptor, murine delta opioid receptor, murine mu opioid receptor, or ORL-1.  
     
     
         5 . Recombinant host cells modified to contain the expression system of  claim 3 .  
     
     
         6 . A method to produce an opioid receptor protein which method comprises culturing the cells of  claim 5  under conditions that effect expression of the encoding DNA to produce said receptor protein, and 
 recovering the receptor protein from the culture.  
 
     
     
         7 . A method to produce recombinant cells that display opioid receptors at their surface, which method comprises culturing the cells of  claim 5  under conditions that effect expression of the encoding DNA to produce said receptor protein at their surface.  
     
     
         8 . Recombinant cells prepared by the method of  claim 7 .  
     
     
         9 . A method to screen a candidate substance for opioid agonist or antagonist activity, which method comprises: 
 incubating the cells of  claim 8  in the presence and absence of the candidate substance under conditions suitable for detection of such activity, and    detecting the presence, absence or amount of said activity.    
     
     
         10 . An opioid receptor produced by the method of  claim 6 .  
     
     
         11 . An antibody composition free of red blood cells which comprises antibodies immunoreactive with the opioid receptor produced by the method of  claim 6 .  
     
     
         12 . A method for determining anatomical locations of opioid receptors in vertebrates, which method comprises: 
 administering the antibody composition of  claim 11  to a vertebrate subject;    waiting a sufficient time for said antibody composition to complex with said receptor; and    detecting the location of said complex in said subject.    
     
     
         13 . A method for blocking the interaction of opioids with opioid receptors which method comprises: 
 contacting said receptors with the antibody composition of claim  11 ; and    allowing said composition to bind to said receptor.    
     
     
         14 . A method to modulate the expression of DNA encoding an opioid receptor which method comprises treating a cell capable of such expression with a DNA complementary to the DNA of  claim 1  under conditions wherein said DNA of  claim 1  hybridizes to said target DNA.