Protease-activated receptor-2 in endosomes signals persistent pain of irritable bowel syndrome.

ABSTRACT: Once activated at the surface of cells, G protein-coupled receptors (GPCRs) redistribute to endosomes, where they can continue to signal. Whether GPCRs in endosomes generate signals that contribute to human disease is unknown. We evaluated endosomal signaling of protease-activated receptor-2 (PAR₂), which has been proposed to mediate pain in patients with irritable bowel syndrome (IBS). Trypsin, elastase, and cathepsin S, which are activated in the colonic mucosa of patients with IBS and in experimental animals with colitis, caused persistent PAR₂-dependent hyperexcitability of nociceptors, sensitization of colonic afferent neurons to mechanical stimuli, and somatic mechanical allodynia. Inhibitors of clathrin- and dynamin-dependent endocytosis and of mitogen-activate

SUBMITTER: Jimenez-Vargas NN 

PROVIDER: S-EPMC6077730 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature