TRPA1 and TRPV1 Receptors Protect the Gastric Mucosa from Ethanol-Induced Injury: Evidence from Knockout Mice

Ethanol disrupts gastric mucosal integrity and induces inflammation. Transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) are receptors expressed in the gastrointestinal tract, but their role in gastric protection against ethanol-induced injury remains unclear. This study investigated the contribution of TRPA1 and TRPV1 to gastric responses following ethanol exposure. Wild-type mice and mice lacking TRPA1, TRPV1, or both receptors were subjected to intragastric ethanol administration. Gastric injury was evaluated by macroscopic and histologic analysis. Messenger RNA expression of selected proinflammatory cytokines and receptor transcripts was quantified using quantitative polymerase chain reaction. Receptor localization was examined by double immunofluorescence and confocal microscopy. Ethanol administration induced pronounced gastric mucosal injury in receptor-deficient mice, whereas only minimal changes were observed in wild-type animals. The protective effect was gradational, with weaker protection associated with TRPV1, greater protection with TRPA1, and the strongest protection when both receptors were present, suggesting a combined contribution of both receptors. In wild-type animals, ethanol exposure induced time-dependent changes in receptor expression, suggesting adaptive regulation. Immunofluorescence revealed localization of both receptors in neuronal and non-neuronal structures of the gastric wall. These findings demonstrate the distinct roles of TRPA1 and TRPV1 in protecting the gastric mucosa against ethanol-induced injury.