Natural ligand of orphan G protein coupled receptor GPR86 and methods of use

A method of screening for a candidate modulator of GPR86 activity using cells expressing GPR86, said method compromising:

• a) incubating a first sample of said cells in the presence of said candidate modulator and a second sample of said cells in the absence of said candidate modulator, both said samples under conditions which permit binding of ADP to GPR86;
• b) detecting a signalling activity of GPR86 polypeptide in said first and second samples, and
• c) comparing the results of said second messenger assays for said first and second samples.

A method of screening for a candidate modulator of GPR86 activity using cell membranes bearing GPR86, said method comprising:

• a) incubating a first sample of said cell membranes in the presence of said candidate modulator and a second sample of said cell membranes in the absence of said candidate modulator, both said samples under conditions which permit binding of ADP to GPR86;
• b) detecting a signalling activity of GPR86 polypeptide in said first and second samples, and
• c) comparing the results of said second messenger assays for said first and second samples.

A method for determining if a candidate modulator increases or decreases the activity of GPR86 using cells expressing GPR86, said method comprising:

• a) incubating a first sample of said cells in the presence of said candidate modulator and a second sample of said cells in the absence of said candidate modulator, both said samples under conditions which permit binding of ADP to GPR86;
• b) detecting a signalling activity of GPR86 polypeptide in said first and second samples, and
• c) comparing the results of said second messenger assays for said first and second samples.

A method for determining if a candidate modulator increases or decreases the activity of GPR86 using cell membranes bearing GPR86, said method comprising:

• a) incubating a first sample of said cell membranes in the presence of said candidate modulator and a second sample of said cell membranes in the absence of said candidate modulator, both said samples under conditions which permit binding of ADP to GPR86;
• b) detecting a signalling activity of GPR86 polypeptide in said first and second samples, and
• c) comparing the results of said second messenger assays for said first and second samples.

A kit for detecting binding to GPR86 or a modulator of GPR86, said kit comprising GPR86 and ADP, and packaging materials therefore, wherein said GPR86 and ADP are packaged separately.

A non-human mammal comprising a partial or total deletion of the ortholog sequence of the human polynucleotide (SEQ ID NO.1), preferably a non-human mammal comprising a homologous recombinant knockout of said polynucleotide or a transgenic non-human mammal overexpressing above natural level said polynucleotide.

A method of identifying an agent that modulates the function of GPR86, said method comprising:

• a) contacting a GPR86 polypeptide with ADP in the presence and absence of a candidate modulator under conditions permitting the binding of said ADP to said GPR86 polypeptide;
• and
• b) measuring the binding of said GPR86 polypeptide to said candidate modulator, relative to the binding in the absence of said candidate modulator, identifies said candidate modulator as an agent that modulates the function of GPR86.

A method of modulating the activity of a GPR86 polypeptide in a cell, said method comprising the step of delivering to said cell an agent that modulates the activity of a GPR86 polypeptide, such that the activity of GPR86 is modulated.

An antibody specific for a GPR86 polypeptide.

A kit for screening for agents that modulate the signalling activity of GPR86, said kit comprising an isolated polynucleotide encoding a GPR86 polypeptide and means for detecting GPR86 signalling, and packaging materials therefore.

A kit for screening for agents that modulate the signalling activity of GPR86, said kit comprising a cell transformed with a polynucleotide encoding a GPR86 polypeptide and means for detecting GPR86 signalling, and packaging materials therefore.

A kit for the diagnosis of a disease or disorder characterized by dysregulation of GPR86 signalling, said kit comprising an isolated GPR86 polypeptide and means for detecting GPR86 signalling, and packaging materials therefore.