Raboin Shannon J, Reeve Joseph R, Cooper Marvis S, Green Gary M, Sayegh Ayman I
Gastroenterology Laboratory, Department of Biomedical Sciences, College of Veterinary Medicine, Tuskegee University, Tuskegee, Alabama, United States.
Regul Pept. 2008 Oct 9;150(1-3):73-80. doi: 10.1016/j.regpep.2008.06.007. Epub 2008 Jun 23.
It has been shown in the rat that endogenous cholecystokinin (CCK), released in response to the non-nutrient trypsin inhibitor camostat, reduces food intake at meals and increases Fos-like immunoreactivity (Fos-LI; a marker for neuronal activation) in the dorsal vagal complex (DVC) of the hindbrain but not the myenteric plexus of the duodenum and jejunum. Experiment 1: We examined Fos-LI in the myenteric and the submucosal plexuses of the gut in response to orogastric gavage of camostat in rats. As we reported previously, camostat failed to increase Fos-LI in the myenteric plexus. We show here that camostat increased Fos-LI in the submucosal plexus of the duodenum and jejunum. Camostat also increased Fos-LI in the DVC. Experiment 2: Pretreatment with devazepide, a specific CCK(1) receptor antagonist abolished camostat-induced Fos-LI in the submucosal plexus and the DVC. Experiment 3: Bilateral subdiaphragmatic vagotomy reduced camostat-induced Fos-LI in the submucosal plexus approximately 40% and abolished it in the DVC.
Activation of the submucosal plexus by cholecystokinin at the CCK(1) receptor accompanies stimulation of the dorsal vagal complex of the hindbrain and inhibition of food intake. Unlike the submucosal plexus, activation of the myenteric plexus is not necessary for cholecystokinin's influence on the dorsal vagal complex and food intake. The lack of activation in the myenteric plexus after camostat stimulation, in contrast to nutrient releasers of CCK such as oleate, suggests that intestinal stimulants can either release different amounts of CCK or cause release of CCK from I cells with different molecular forms of CCK. This would suggest that CCK-8 is released by camostat and is not able to travel to the myenteric plexus while a more stable form of CCK such as CCK-58 can travel to this site that is further away from the I cell.
在大鼠实验中已表明，内源性胆囊收缩素（CCK）在对非营养性胰蛋白酶抑制剂抑肽酶产生反应时释放，可减少进餐时的食物摄入量，并增加后脑背迷走神经复合体（DVC）中的Fos样免疫反应性（Fos-LI；神经元激活的标志物），但不会增加十二指肠和空肠肌间神经丛中的Fos-LI。实验1：我们检测了大鼠经口胃管灌注抑肽酶后，肠道肌间神经丛和黏膜下神经丛中的Fos-LI。正如我们之前报道的，抑肽酶未能增加肌间神经丛中的Fos-LI。我们在此表明，抑肽酶增加了十二指肠和空肠黏膜下神经丛中的Fos-LI。抑肽酶还增加了DVC中的Fos-LI。实验2：用特异性CCK(1)受体拮抗剂德瓦西匹进行预处理，可消除抑肽酶诱导的黏膜下神经丛和DVC中的Fos-LI。实验3：双侧膈下迷走神经切断术使抑肽酶诱导的黏膜下神经丛中的Fos-LI降低约40%，并消除了DVC中的Fos-LI。
胆囊收缩素通过CCK(1)受体激活黏膜下神经丛，同时刺激后脑背迷走神经复合体并抑制食物摄入。与黏膜下神经丛不同，肌间神经丛的激活对于胆囊收缩素对背迷走神经复合体和食物摄入的影响并非必需。与CCK的营养释放剂（如油酸）相比，抑肽酶刺激后肌间神经丛缺乏激活，这表明肠道刺激剂要么释放不同量的CCK，要么导致具有不同分子形式CCK的I细胞释放CCK。这表明抑肽酶释放CCK-8，且其无法到达肌间神经丛，而更稳定形式的CCK（如CCK-58）可以到达离I细胞更远的该部位。
