Des-acyl ghrelin acts by CRF type 2 receptors to disrupt fasted stomach motility in conscious rats
Des-acyl ghrelin acts by CRF type 2 receptors to disrupt fasted stomach motility in conscious rats
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DOI：
10.1053/j.gastro.2005.04.015
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发表时间：
2005-07-01
期刊：
影响因子：
29.4
通讯作者：
Fujimiya, M
中科院分区：
文献类型：
--
作者：
Chen, CY;Inui, A;Fujimiya, M
背景和目标：尽管已经表明去酰基生长素释放肽减少食物摄入和胃排空，但是先前没有研究检查去酰基生长素释放肽对胃肠道中的生理性进食和禁食运动活动的影响。研究方法：我们研究了腹膜内（IP）给药的des-acyl ghrelin对食物摄入量的影响，以及脑室内（ICV）或静脉内（IV）给药的des-acyl ghrelin对胃十二指肠运动的影响，使用自由活动的清醒大鼠模型。脑切片用c-fos免疫组织化学方法检测脑内对这些效应作出反应的核团。结果：IP注射去酰基生长素释放肽减少食物摄入量，辣椒素治疗没有改变这种效果。IP注射去酰基ghrelin增强了弓状核和室旁核的c-fos表达，但在孤束核中没有。ICV和IV注射去酰基ghrelin均破坏了胃窦的禁食运动活动，但未破坏十二指肠。IV注射去酰基ghrelin引起的胃运动变化可被ICV注射选择性促肾上腺皮质激素释放因子（CRF）（2）受体拮抗剂完全拮抗;然而，CRF 1受体拮抗剂无作用。结论：结果表明，去酰基ghrelin减少食物的摄入量，扰乱了空腹运动活动的自由活动清醒大鼠的胃窦。外周去酰基ghrelin可能通过直接激活脑受体而不是通过激活迷走神经传入通路，穿过血脑屏障来诱导这种功能。在大脑中，CRF 2受体，而不是CRF 1。受体，参与了这一行动。
Background & Aims: Although it has been shown that des-acyl ghrelin decreases food intake and gastric emptying, no previous studies have examined the effects of des-acyl ghrelin on physiologic fed and fasted motor activity in the gastrointestinal tract. Methods: We examined the effects of intraperitoneal (IP) administration of des-acyl ghrelin on food intake and the effects of intracerebroventricular (ICV) or intravenous (IV) administration of des-acyl ghrelin on gastroduodenal motility using freely moving conscious rat models. The brain nuclei responding to these effects were examined by c-fos immunohistochemistry of the brain sections. Results: IP injection of des-acyl ghrelin decreased food intake, and this effect was not altered by capsaicin treatment. IP injection of des-acyl ghrelin enhanced c-fos expression in the arcuate and paraventricular nucleus but not in the nucleus of the solitary tract. Both ICV and IV injection of des-acyl ghrelin disrupted fasted motor activity in the antrum but not in the duodenum. Changes in gastric motility induced by IV injection of des-acyl ghrelin were completely antagonized by ICV injection of a selective corticotropin-releasing factor (CRF)(2) receptor antagonist; however, the CRF1 receptor antagonist had no effects. Conclusions: The results suggest that des-acyl ghrelin decreases food intake and disrupts the fasted motor activity of the antrum in freely moving conscious rats. Peripheral des-acyl ghrelin may induce this function by direct activation of brain receptor by crossing the blood-brain barrier but not by the activation of vagal afferent pathways. In the brain, CRF2 receptor, but not CRF1. receptor, is involved in this action.