Neuropeptide receptor and uses thereof
AssigneePfizer Inc.
InventorsNicola Melanie Robas, Mark David Fidock
Life of this patent
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Abstract
This invention relates to the identification of an orphan G-protein coupled receptor MRGX2 (and variants thereof) as a receptor of neuropeptides such as but not limited to cortistatin, somatostatin, Bam 13-22, α-MSH, neuropeptide FF, dynorphin A and substance P, and the use of such neuropeptides (and structurally related molecules) as modulators for MRGX2. It also relates to screening methods to identify agonists and antagonists for this neuropeptide receptor.
Claims21
Use of cortistatin, somatostatin, Bam 13-22, α-MSH, neuropeptide FF, dynorphin A or substance P or an analogue or mimetic of any one of these neuropeptides as a ligand for receptor MRGX2.
Use of cortistatin, somatostatin, Bam 13-22, α-MSH, neuropeptide FF, dynorphin A or substance P or an analogue or mimetic of any one of these neuropeptides as a modulator for receptor MRGX2.
Use of cortistatin, somatostatin, Bam 13-22, α-MSH, neuropeptide FF, dynorphin A or substance P or an analogue or mimetic of any one of these neuropeptides to elicit a functional response on receptor MRGX2.
A method of screening for compounds that are modulators of receptor MRGX2, using cortistatin, somatostatin, Bam 13-22, α-MSH, neuropeptide FF, dynorphin A or substance P or an analogue or mimetic of any one of these neuropeptides as ligand.
A method of screening for compounds that are modulators of a novel neuropeptide receptor, including but not limited to the following steps:
- (a) contacting a sample of receptor MRGX2 with a ligand selected from cortistatin, somatostatin, Bam 13-22, α-MSH, neuropeptide FF, dynorphin A or substance P or an analogue or mimetic of any one of these neuropeptides;
- (b) contacting a similar sample of receptor MRGX2 or membranes prepared from said cells with both the ligand used in step (a) and a test compound or mixture of test compounds;
- (c) comparing the results of (a) and (b) to determine whether the binding of the ligand used is affected by the presence of the test compound or mixture of test compounds.
A method of screening for compounds that are modulators of a novel neuropeptide receptor, including but not limited to the following steps:
- (a) contacting a sample of receptor MRGX2 with a ligand selected from cortistatin, somatostatin, Bam 13-22, α-MSH, neuropeptide FF, dynorphin A or substance P or an analogue or mimetic of any one of these neuropeptides, with a detectable label attached;
- (b) contacting a similar sample of receptor MRGX2 or membranes prepared from said cells with both the labelled ligand used in step (a) and a test compound or mixture of test compounds;
- (c) comparing the amount of label bound in (a) and (b) to determine whether the binding of the ligand used is affected by the presence of the test compound or mixture of test compounds.
A method of expressing a novel neuropeptide receptor, comprising transferring a suitable expression vector comprising SEQ ID NO:
- 1 or variants or homologues thereof, into suitable host cells, and culturing said host cells under conditions suitable for the expression of the receptor.
A method of expressing a novel neuropeptide receptor, comprising upregulating the expression of MRGX2 in a suitable cell.
A method for screening for agonists of a novel neuropeptide receptor, comprising the steps:
- (a) adding a test compound or a mixture of test compounds to suitable cells expressing MRGX2,
- (b) measuring whether a functional response is seen.
A method of diagnosing a novel neuropeptide-receptor-mediated disorder in a mammal, comprising
- (a) measuring the level of MRGX2 gene expression, or
- (b) measuring the neuropeptide-dependent activity of MRGX2
- in a patient sample, and comparing said measurement to that determined from clinically normal individuals.
Dependencies are inferred from the claim text.