Mrgprx2

mast cell receptor which has been identified as the cause of pseudoallergic drug reactions . The coding receptor gene is located on chromosome 11p15.1. MRGPRX2 is expressed in high concentrations in human skin mast cells, synovial MCs, but not in lung MCs (HLMCs) (Tatemoto et al. 2006; McNeil et al. 2015).

MRGPRX2 acts as a specific mast cell receptor for cationic amphiphilic drugs and endo- or exogenous peptides. The specific mast cell receptor recognizes and binds small molecules containing cyclized tetrahydroisoquinoline (THIQ), such as non-steroidal neuromuscular blockers (NMBDs), including Tubocurarine and Atracurium. Furthermore, drugs such as morphine, vancomycin and ciprofloxacin are able to specifically bind to this receptor and activate it.

The activation of this mast cell receptor leads to degranulation in human mast cells. Depending on the extent of activation, this can lead to pseudoallergic reactions(histamine release, inflammation and contraction of the airways). Furthermore, MRGPRX2 acts as a receptor for a number of other ligands, such as peptides and alkaloids (cortistatin-14, proadrenomedullin N-terminal peptides PAMP-12, to a lesser extent also PAMP-20, antibacterial protein LL-37, PMX-53 peptide, beta-defensins and complanadine A). There is also increasing evidence that mast cells and their mediators play a role in neurogenic inflammation leading to pain and itching (Steinhoff et al.2018). Another clinical relevance is that MRGPRX2 is overexpressed in skin mast cells of patients with chronic urticaria (Gaudenzio et al. 2016).

1. Gaudenzio N et al (2016) Different activation signals induce distinct mast cell degranulation strategies. J Clin Invest 126: 3981-3998.
2. McNeil B D et al (2015) Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature 519: 237-241.
3. Navinés-Ferrer A et al (2018) MRGPRX2-mediated mast cell response to drugs used in perioperative procedures and anaesthesia. Sci Rep PMID 30072729
4. Steinhoff M et al (2000) Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat Med 6:151-158.
5. Tatemoto K et al (2006) Immunoglobulin E-independent activation of mast cell is mediated by Mrg receptors. Biochem Biophys Res Commun 349: 1322-1328.