Deoxycholic acid activates colonic afferent nerves via 5-HT 3 receptor-dependent and -independent mechanisms

作者：Yang Yu, Egina C. Villalobos-Hernández, Sabindra Pradhananga, Corey C. Baker, Christopher Keating, David Grundy, Alan Lomax, David E. Reed · 发表于：American Journal of Physiology-Gastrointestinal and Liver Physiology · 年份：2019 · DOI：10.1152/ajpgi.00016.2019 · 被引用次数：32 · 研究领域：Gastrointestinal motility and disorders、Gastroesophageal reflux and treatments、Pain Mechanisms and Treatments

Increased bile acids in the colon can evoke increased epithelial secretion resulting in diarrhea, but little is known about whether colonic bile acids contribute to abdominal pain. This study aimed to investigate the mechanisms underlying activation of colonic extrinsic afferent nerves and their neuronal cell bodies by a major secondary bile acid, deoxycholic acid (DCA). All experiments were performed on male C57BL/6 mice. Afferent sensitivity was evaluated using in vitro extracellular recordings from mesenteric nerves in the proximal colon (innervated by vagal and spinal afferents) and distal colon (spinal afferents only). Neuronal excitability of cultured dorsal root ganglion (DRG) and nodose ganglion (NG) neurons was examined with perforated patch clamp. Colonic 5-HT release was assessed using ELISA, and 5-HT immunoreactive enterochromaffin (EC) cells were quantified. Intraluminal DCA increased afferent nerve firing rate concentration dependently in both proximal and distal colon. This DCA-elicited increase was significantly inhibited by a 5-HT 3 antagonist in the proximal colon but not in the distal colon, which may be in part due to lower 5-HT immunoreactive EC cell density and lower 5-HT levels in the distal colon following DCA stimulation. DCA increased the excitability of DRG neurons, whereas it decreased the excitability of NG neurons. DCA potentiated mechanosensitivity of high-threshold spinal afferents independent of 5-HT release. Together, this study suggests that...