MRGPRX2-Mediated Degranulation of Human Skin Mast Cells Requires the Operation of G_αi, G_αq, Ca++ Channels, ERK1/2 and PI3K-Interconnection between Early and Late Signaling.

ABSTRACT: The recent discovery of MRGPRX2 explains mast cell (MC)-dependent symptoms independently of FcεRI-activation. Because of its novelty, signaling cascades triggered by MRGPRX2 are rudimentarily understood, especially in cutaneous MCs, by which MRGPRX2 is chiefly expressed. Here, MCs purified from human skin were used following preculture or ex vivo and stimulated by FcεRI-aggregation or MRGPRX2 agonists (compound 48/80, Substance P) in the presence/absence of inhibitors. Degranulation was assessed by β-hexosaminidase or histamine release. Phosphorylation events were studied by immunoblotting. As a G protein-coupled receptor, MRGPRX2 signals by activating G proteins; however, their nature has remained controversial. In skin MCs, G_αi and G_αq were required for degranulatio

SUBMITTER: Wang Z 

PROVIDER: S-EPMC8946553 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature