Castex N, Fioramonti J, Fargeas M J, Bueno L
Department of Pharmacology, INRA, Toulouse, France.
Brain Res. 1995 Aug 7;688(1-2):149-60. doi: 10.1016/0006-8993(95)00526-v.
The c-fos immediate-early gene is acutely induced in brain after various stimuli from the digestive tract. 5-HT3 receptors and vagal afferents have been found involved in intestinal motor disturbances induced by intestinal anaphylaxis. Our aim was to determine whether intestinal anaphylaxis activates brain structures, using c-fos expression, and to evaluate the modulation of c-fos induction by 5-HT3 receptors and vagal afferents. The effects of antigen challenge on intestinal motility were evaluated in ovalbumin-sensitized Hooded Lister rats chronically fitted with NiCr electrodes in the jejunal wall. Intestinal motility was assessed in conscious rats pretreated or not by perivagal capsaicin or a 5-HT3 antagonist (ondansetron). In sensitized rats, ovalbumin disrupted for 62.4 +/- 9.5 min the jejunal migrating motor complexes (MMC) and an important c-fos expression was detected in the nucleus tractus solitarius (NTS), lateral parabrachial nucleus (LPB) and paraventricular nucleus of the hypothalamus (PVN). Intraperitoneal administration of ondansetron or perivagal capsaicin treatment significantly reduced the duration of MMC disruption and attenuated markedly c-fos staining in the 3 brain sites. In contrast, intracerebroventricular administration of ondansetron significantly reduced jejunal motor alterations but did not diminish the c-fos expression, suggesting a role of central 5-HT3 receptors in the efferent control of the intestinal disturbances. Blockade of both c-fos expression and MMC disruption by systemic ondansetron and by perivagal capsaicin indicates that some brainstem nuclei are involved in digestive disturbances after intestinal anaphylaxis, and reflects an involvement of peripheral 5-HT3 receptors on vagal afferents. The reduction of c-fos staining in NTS as well as in LPB and PVN after perivagal capsaicin suggests that the NTS is the primary relay in the activation of the central nervous system during intestinal allergic challenge.
在受到来自消化道的各种刺激后，即刻早期基因c-fos会在大脑中被急性诱导。已发现5-羟色胺3（5-HT3）受体和迷走神经传入纤维参与了肠道过敏反应引起的肠道运动障碍。我们的目的是利用c-fos表达来确定肠道过敏反应是否会激活脑结构，并评估5-HT3受体和迷走神经传入纤维对c-fos诱导的调节作用。在长期于空肠壁植入镍铬电极的卵清蛋白致敏的带帽利斯特大鼠中，评估抗原激发对肠道运动的影响。在经迷走神经周围注射辣椒素或5-HT3拮抗剂（昂丹司琼）预处理或未预处理的清醒大鼠中评估肠道运动。在致敏大鼠中，卵清蛋白使空肠移行性运动复合波（MMC）中断62.4±9.5分钟，并且在孤束核（NTS）、外侧臂旁核（LPB）和下丘脑室旁核（PVN）中检测到重要的c-fos表达。腹腔注射昂丹司琼或迷走神经周围辣椒素处理显著缩短了MMC中断的持续时间，并明显减弱了这3个脑区的c-fos染色。相比之下，脑室内注射昂丹司琼显著减轻了空肠运动改变，但并未减少c-fos表达，这表明中枢5-HT3受体在肠道紊乱的传出控制中起作用。全身应用昂丹司琼和迷走神经周围辣椒素对c-fos表达和MMC中断的阻断表明，某些脑干核参与了肠道过敏反应后的消化紊乱，并且反映了外周5-HT3受体对迷走神经传入纤维的参与。迷走神经周围辣椒素处理后NTS以及LPB和PVN中c-fos染色的减少表明，NTS是肠道过敏激发期间中枢神经系统激活的主要中继站。
