MrgX2 is a high potency cortistatin receptor expressed in dorsal root ganglion.
MrgX2 is a recently identified orphan G-protein-coupled receptor whose ligand and physiological function were unknown. Here we describe cortistatin, a neuropeptide for which no specific receptor has been identified previously, as a high potency ligand at MrgX2. Cortistatin has several biological functions including roles in sleep regulation, locomotor activity, and cortical function. Using a "reverse pharmacology" approach, we have identified a number of additional cyclic peptide agonists for MrgX2, determined their rank order of potency, and demonstrated that this receptor has a pharmacological profile distinct from the other characterized members of the Mrg (Mas-related genes) family. In MrgX2-expressing cells, cortistatin-stimulated increases in intracellular Ca2+ but had no effect on basal or forskolin-stimulated cAMP levels, suggesting that this receptor is Gq-coupled. Immunohistochemical and quantitative PCR studies show MrgX2 to have a limited expression profile, both peripheral and within the central nervous system, with highest levels in dorsal root ganglion.
Robas
Nicola
N
Department of Target Genomics, Pfizer Global Research and Development, Sandwich, Kent, CT13 N9J, United Kingdom.
Mead
Emma
E
Fidock
Mark
M
D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005727:Ganglia, Spinal / Q000737:chemistry*; D015870:Gene Expression; D006624:Hippocampus / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000737:chemistry; D009479:Neuropeptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D014018:Tissue Distribution; D014162:Transfection
D008024:Ligands; C480039:MRGPRX2 protein, human; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D010456:Peptides, Cyclic; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; C467796:cortistatin 14; D005576:Colforsin; D000242:Cyclic AMP; D002118:Calcium