Novel receptor

Abstract

The present invention relates to the novel GABA B receptor subtypes GABA B -R1c and GABA B -R2 as well as to a novel, functional GABA B receptor which comprises a heterodimer of GABA B -R1 and GABA B -R2 receptor subunits. The present invention also relates to variants of the receptors, nucleotide sequences encoding the receptors and variants thereof and novel vectors, stable cell lines, antibodies, screening methods, methods of treatment and methods of receptor production.

1 . An isolated GABA B -R2 receptor protein or a variant thereof.  
     
     
         2 . An isolated GABA B -R2 receptor protein having amino acid sequence provided in FIG. 1B, or a variant thereof.  
     
     
         3 . A nucleotide sequence encoding a GABA B -R2 receptor or a variant thereof, or a nucleotide sequence which is complementary thereto.  
     
     
         4 . The nucleotide sequence of  claim 3  which is a cDNA sequence.  
     
     
         5 . A nucleotide sequence encoding a GABA B -R2 receptor, as shown in FIG. 1A, or a variant thereof, or a nucleotide sequence which is complementary thereto.  
     
     
         6 . The nucleotide sequence of  claim 4  which is a cDNA sequence.  
     
     
         7 . An expression vector comprising the nucleotide sequence of  claim 3 , which is capable of expressing a GABA B -R2 receptor protein or a variant thereof.  
     
     
         8 . An expression vector comprising the nucleotide sequence of  claim 5 , which is capable of expressing a GABA B -R2 receptor protein or a variant thereof.  
     
     
         9 . A stable cell line comprising a vector according to  claim 7 .  
     
     
         10 . The cell line according to  claim 9  which is a modified HEK293T cell line.  
     
     
         11 . An antibody specific for a protein as claimed in  claim 1 .  
     
     
         12 . An antibody specific for a protein as claimed in  claim 2 .  
     
     
         13 . An isolated GABA B -R1c receptor protein or a variant thereof.  
     
     
         14 . An isolated GABA B -R1c receptor protein having amino acid sequence provided in FIG. 2, or a variant thereof.  
     
     
         15 . A nucleotide sequence encoding a GABA B -R1c receptor protein or a variant thereof, or a nucleotide sequence which is complementary thereto.  
     
     
         16 . A nucleotide sequence of  claim 15  which is a cDNA sequence.  
     
     
         17 . A nucleotide sequence encoding a GABA B -R1c receptor protein or a variant thereof as claimed in  claim 14 , or a nucleotide sequence which is complementary thereto.  
     
     
         18 . A nucleotide sequence of  claim 17  which is a cDNA sequence.  
     
     
         19 . An expression vector comprising the nucleotide sequence of  claim 15 , which is capable of expressing a GABA B -R1c receptor protein or a variant thereof.  
     
     
         20 . A stable cell line comprising the vector according to  claim 19 .  
     
     
         21 . The cell line according to  claim 20  which is a modified HEK293T cell line.  
     
     
         22 . An antibody specific for the protein claimed in  claim 13 .  
     
     
         23 . An antibody specific for the protein claimed in  claim 14 .  
     
     
         24 . A GABA B  receptor comprising an heterodimer between a GABA B -R1 receptor protein or a variant thereof and a GABA B -R2 receptor protein or a variant thereof.  
     
     
         25 . The GABA B  receptor according to  claim 24  wherein the GABA B -R1 receptor is a GABA B -R1a receptor or variant thereof.  
     
     
         26 . The GABA B  receptor according to  claim 24  wherein the GABA B -R1 receptor is a GABA B -R1b receptor or variant thereof.  
     
     
         27 . The GABA B  receptor according to  claim 24  wherein the GABA B -R1 receptor is a GABA B -R1c receptor or variant thereof.  
     
     
         28 . An expression vector comprising a nucleotide sequence encoding for a GABA B -R1 receptor or a variant thereof and a nucleotide sequence encoding for a GABA B -R2 receptor or variant thereof, said vector being capable of expressing both a GABA B -R1 and a GABA B -R2 receptor proteins or variants thereof.  
     
     
         29 . The vector according to  claim 28  wherein the GABA B -R1 receptor is a GABA B -R1a receptor or variant thereof.  
     
     
         30 . The vector according to  claim 28  wherein the GABA B -R1 receptor is a GABA B -R1b receptor or variant thereof.  
     
     
         31 . The vector according to  claim 28  wherein the GABA B -R1 receptor is a GABA B -R1c receptor or variant thereof.  
     
     
         32 . A stable cell line comprising a vector according to  claim 28 .  
     
     
         33 . The stable cell line according to  claim 32  which is a modified HEK293T cell line.  
     
     
         34 . A stable cell line modified to express both GABA B -R1 and GABA B -R2 receptor proteins or variants thereof.  
     
     
         35 . The stable cell line according to  claim 34  which is a modified HEK293T cell line.  
     
     
         36 . A GABA B  receptor produced by the stable cell line of  claim 34 .  
     
     
         37 . An antibody specific for the receptor as claimed in  claim 24 .  
     
     
         38 . A method for identification of a compound which exhibits GABA B  receptor modulating activity, comprising contacting the GABA B  receptor of  claim 24  with a test compound and detecting modulating activity or inactivity.  
     
     
         39 . A compound which modulates GABA B  receptor activity, identifiable by a method according to  claim 38 .  
     
     
         40 . A method of treatment or prophylaxis of a disorder which is responsive to modulation of GABA B  receptor activity in a mammal, which comprises administering to said mammal an effective amount of a compound identifiable by the method according to  claim 38 .  
     
     
         41 . The method according to  claim 40  wherein the disorder is a CNS disorder, a GI disorder, a lung disorder or a bladder disorder.  
     
     
         42 . The method according to  claim 40  wherein the disorder is spasticity, epilepsy, Alzheimer's disease, pain or an affective or feeding disorder.  
     
     
         43 . Use of a compound identifiable by the method according to  claim 38  in a method of formulating a medicament for treatment or prophylaxis of a disorder which is responsive to modulation of GABA B  receptor activity in a mammal.  
     
     
         44 . The use according to  claim 43  wherein the disorder is a CNS disorder, a GI disorder, a lung disorder or a bladder disorder.  
     
     
         45 . The use according to  claim 43  wherein the disorder is spasticity, Alzheimer's disease, pain or an affective or feeding disorder.  
     
     
         46 . A method of producing a GABA B  receptor comprising introducing into an appropriate cell line a suitable vector or vectors comprising nucleotide sequences encoding for GABA B -R1 and GABA B -R2 receptors or variants thereof, under conditions suitable for obtaining expression of the receptors or variants.