Regulatory Mechanism of the Gastric Hyperemic Response Following Barrier Disruption: Roles of Cyclooxygenase-1, the Prostaglandin E₂/EP1 Receptor and Sensory Neurons

Title:Regulatory Mechanism of the Gastric Hyperemic Response Following Barrier Disruption: Roles of Cyclooxygenase-1, the Prostaglandin E₂/EP1 Receptor and Sensory Neurons

Volume: 21 Issue: 21

Author(s): Koji Takeuchi, Masanori Takeeda, Kikuko Amagase and Masato Nakashima

Affiliation:

Keywords: Barrier disruption, bile acids, cyclooxygenase isozyme, EP receptors, gastric mucosal blood flow, gastric damage, prostaglandins, sensory neurons.

Abstract: We herein reviewed the mechanism underlying the gastric hyperemic response following barrier disruption, with a focus on cyclooxygenase (COX) isozymes, prostaglandin (PG) E₂, and capsaicin-sensitive afferent neurons. Mucosal damage was induced by exposing the stomach to 20 mM taurocholate (TC) with 50 mM HCl. The TC treatment disrupted surface epithelial cells, and then increased acid back-diffusion and mucosal blood flow (GMBF) in the stomachs of rats or wild-type mice. This hyperemic response in the rat stomach was inhibited by indomethacin without affecting acid back-diffusion, which resulted in the aggravation of lesions. The effect of indomethacin was mimicked by loxoprofen and the selective COX-1 inhibitor, SC-560, but not by the selective COX-2 inhibitor, celecoxib. The GMBF responses induced by TC were similarly observed in the stomachs of wild-type mice and EP3 receptor knockout mice, but not in mice lacking the EP1 receptor or pretreated with an EP1 antagonist. The increase in the GMBF response associated with acid back-diffusion after the TC treatment was also inhibited by the chemical ablation of capsaicin-sensitive afferent neurons, but not capsazepine, a TRPV1 antagonist. Thus, endogenous PGE₂ produced by COX-1 plays a role in the gastric hyperemic response following barrier disruption of the stomach by interacting with capsaicin-sensitive afferent neurons, mainly through EP1 receptors, and facilitating the GMBF response to acid back-diffusion. These findings have also contributed to a deeper understanding of mucosal defensive mechanisms following barrier disruption and the development of new strategies for the treatment of gastrointestinal diseases.

Cite this article as:

Takeuchi Koji, Takeeda Masanori, Amagase Kikuko and Nakashima Masato, Regulatory Mechanism of the Gastric Hyperemic Response Following Barrier Disruption: Roles of Cyclooxygenase-1, the Prostaglandin E₂/EP1 Receptor and Sensory Neurons, Current Pharmaceutical Design 2015; 21 (21) . https://dx.doi.org/10.2174/1381612821666150514105248