CDB15:0000366 CORT — MRGPRX2
Experimentally validated in Human; Orthology-inferred in Mouse, Rat, Chicken, Macaque, Pig, Cow, Chimp, Marmoset
Title
Journal:; Year Published:
Abstract
MrgX2 is a high potency cortistatin receptor expressed in dorsal root ganglion.
The Journal of biological chemistry, 2003; PubMed, Homo sapiens CORT — Homo sapiens MRGPRX2
ABSTRACT: 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.
Proadrenomedullin N-terminal peptide and cortistatin activation of MrgX2 receptor is based on a common structural motif.
European journal of pharmacology, 2005; PubMed, Homo sapiens CORT — Homo sapiens MRGPRX2
ABSTRACT: The G protein-coupled receptor MrgX2 belongs to the large family of the Mas-related genes or sensory neuron-specific G protein-coupled receptors. The MrgX2 receptor has been shown to be activated by the peptides cortistatin and proadrenomedullin N-terminal peptides (PAMP). Here we investigated the structure activity relationship of PAMP and identified key structural features that are shared with cortistatin and might explain why two apparently unrelated peptides are able to activate a single G protein-coupled receptor.