Department of Physiology and Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao, China.
Department of Pathology, Women's and Children's Hospital Affiliated to Qingdao University, Qingdao, China.
Neuroendocrinology. 2023;113(3):289-303. doi: 10.1159/000526455. Epub 2022 Aug 11.
Calcium-sensitive receptor (CaSR) is expressed in the enteric nervous system of gastrointestinal tract. However, its role in the regulation of gastrointestinal motility has not yet been fully elucidated. We aimed to investigate the effect of the CaSR agonist - R568 on gastric motility and its potential mechanism.
In vivo, R568 was given by gavage to explore gastric emptying with or without capsaicin which specifically blocks the function of vagal afferents; neurotransmitters synthetized in the myenteric plexus of the gastric corpus and antrum were analysed by ELISA and immunofluorescence staining; gastric muscle strips contraction recording and intracellular single unit firing recording were used to study the effect of R568 on muscle strips and myenteric interstitial cells of Cajal (ICCs) ex vitro.
Gastric emptying was inhibited by R568 in Kunming male mice, and capsaicin weakened this effect. The expression of c-fos-positive neurons increased in the nucleus tractus solitarius when R568 was treated. R568 decreased the expression of cholinergic neurons and reduced the synthesis of acetylcholine. Conversely, R568 increased the expression of nitrogenic neurons and enhanced the synthesis of nitric oxide in the myenteric plexus. Ex vitro results showed that R568 inhibited the contraction of the gastric antral muscle strip and suppressed the spontaneous firing activity of pacemaker ICCs.
Activation of the gastrointestinal CaSR inhibited gastric motility in vivo and ex vitro. Transmitting nutrient signals to the brain through the vagal afferent nerve, modulating the cholinergic and nitrergic system in the enteric nervous system, and inhibiting activity of pacemaker ICCs in the myenteric plexus are involved in the mechanism of CaSR in gastric motility suppression.
钙敏感受体（CaSR）在胃肠道的肠神经系统中表达。然而，其在胃肠动力调节中的作用尚未完全阐明。我们旨在研究 CaSR 激动剂 - R568 对胃动力的影响及其潜在机制。
在体内，通过灌胃给予 R568，研究其对胃排空的影响，同时给予辣椒素以特异性阻断迷走传入神经的功能；通过 ELISA 和免疫荧光染色分析胃体和胃窦的肌间神经丛中神经递质的合成；使用胃肌条收缩记录和肠内间质细胞（ICC）的单细胞放电记录研究 R568 对肌肉条和 ICC 离体的影响。
R568 抑制昆明雄性小鼠的胃排空，而辣椒素减弱了这种作用。当给予 R568 时，孤束核中的 c-fos 阳性神经元表达增加。R568 减少了胆碱能神经元的表达并降低了乙酰胆碱的合成。相反，R568 增加了氮能神经元的表达并增强了肌间神经丛中一氧化氮的合成。离体结果表明，R568 抑制了胃窦肌条的收缩并抑制了起搏 ICCs 的自发性放电活动。
激活胃肠道 CaSR 抑制体内和体外的胃动力。通过迷走传入神经向大脑传递营养信号，调节肠神经系统中的胆碱能和氮能系统，并抑制肌间神经丛中起搏 ICCs 的活动，这些都涉及 CaSR 抑制胃动力的机制。
