Ataka Koji, Inui Akio, Asakawa Akihiro, Kato Ikuo, Fujimiya Mineko
Research Institute, Taiko Pharmaceutical Co Ltd, Osaka, Japan.
Am J Physiol Gastrointest Liver Physiol. 2008 May;294(5):G1210-8. doi: 10.1152/ajpgi.00549.2007. Epub 2008 Mar 6.
Obestatin is a novel peptide encoded by the ghrelin precursor gene; however, its effects on gastrointestinal motility remain controversial. Here we have examined the effects of obestatin on fed and fasted motor activities in the stomach and duodenum of freely moving conscious rats. We examined the effects of intravenous (IV) injection of obestatin on the percentage motor index (%MI) and phase III-like contractions in the antrum and duodenum. The brain mechanism mediating the action of obestatin on gastroduodenal motility and the involvement of vagal afferent pathway were also examined. Between 30 and 90 min after IV injection, obestatin decreased the %MI in the antrum and prolonged the time taken to return to fasted motility in the duodenum in fed rats given 3 g of chow after 18 h of fasting. Immunohistochemical analysis demonstrated that corticotropin-releasing factor- and urocortin-2-containing neurons in the paraventricular nucleus in the hypothalamus were activated by IV injection of obestatin. Intracerebroventricular injection of CRF type 1 and type 2 receptor antagonists prevented the effects of obestatin on gastroduodenal motility. Capsaicin treatment blocked the effects of obestatin on duodenal motility but not on antral motility. Obestatin failed to antagonize ghrelin-induced stimulation of gastroduodenal motility. These results suggest that, in the fed state, obestatin inhibits motor activity in the antrum and duodenum and that CRF type 1 and type 2 receptors in the brain might be involved in these effects of obestatin on gastroduodenal motility.
肥胖抑制素是一种由胃饥饿素前体基因编码的新型肽；然而，其对胃肠动力的影响仍存在争议。在此，我们研究了肥胖抑制素对自由活动的清醒大鼠胃和十二指肠在进食和禁食状态下运动活性的影响。我们检测了静脉注射肥胖抑制素对胃窦和十二指肠运动指数百分比（%MI）以及十二指肠III期样收缩的影响。还研究了介导肥胖抑制素对胃十二指肠动力作用的脑机制以及迷走神经传入通路的参与情况。静脉注射后30至90分钟内，肥胖抑制素降低了进食大鼠胃窦的%MI，并延长了十二指肠恢复到禁食状态下动力所需的时间，这些大鼠在禁食18小时后给予3克食物。免疫组织化学分析表明，静脉注射肥胖抑制素可激活下丘脑室旁核中含促肾上腺皮质激素释放因子和尿皮质素-2的神经元。脑室内注射1型和2型促肾上腺皮质激素释放因子受体拮抗剂可阻止肥胖抑制素对胃十二指肠动力的影响。辣椒素处理可阻断肥胖抑制素对十二指肠动力的影响，但对胃窦动力无影响。肥胖抑制素未能拮抗胃饥饿素诱导的胃十二指肠动力刺激。这些结果表明，在进食状态下，肥胖抑制素抑制胃窦和十二指肠的运动活性，且脑中的1型和2型促肾上腺皮质激素释放因子受体可能参与了肥胖抑制素对胃十二指肠动力的这些作用。
