Experimental study reveals that RGS6 deletion enhances cannabinoid-mediated pain relief and motility control in mice with colitis, suggesting a neural target for gut disorders.
Key Points
To determine the role of regulator of G protein signaling 6 (RGS6) in gastrointestinal inflammation, motility disorders, and responsiveness to cannabinoid receptor agonists.
Assessed signaling cascades in vitro using wild-type and RGS6 knock-out Caco-2 cells stimulated with GPCR agonists via qPCR, western blot, and ELISA assays.
Evaluated inflammation, gut transit time, and antinociceptive responses to the cannabinoid agonist WIN 55,212-2 (1 mg/kg ip) in wild-type, global, and epithelial-specific RGS6 knock-out mice with dextran sulfate sodium-induced colitis.
In Caco-2 cells, RGS6 knock-out elevated ERK phosphorylation and enabled WIN 55,212-2 to significantly reduce cAMP levels compared to wild-type cells.
In acute and chronic colitis models, global RGS6 knock-out conferred resistance to stress-induced gut hypermotility and amplified the antinociceptive and transit-prolonging actions of WIN 55,212-2.
Epithelial-specific RGS6 knock-out produced no change in the physiological response to WIN 55,212-2.