GPR35 agonists inhibit TRPA1-mediated colonic nociception through suppression of substance P release.

ABSTRACT:

Abstract

The development of nonopioid analgesics for the treatment of abdominal pain is a pressing clinical problem. To address this, we examined the expression of G i/o -coupled receptors, which typically inhibit nociceptor activation, in colonic sensory neurons. This led to the identification of the orphan receptor GPR35 as a visceral analgesic drug target because of its marked coexpression with transient receptor potential ankyrin 1 (TRPA1), a mediator of noxious mechanotransduction in the bowel. Building on in silico docking simulations, we confirmed that the mast cell stabiliser, cromolyn (CS), and phosphodiesterase inhibitor, zaprinast, are agonists at mouse GPR35, promoting the activation of different G i/o subunits. Pretreatment with either CS or zaprinast significantly att

SUBMITTER: Gupta RA 

PROVIDER: S-EPMC11808708 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature