Chen C Y, Chien E J, Chang F Y, Lu C L, Luo J C, Lee S D
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Peptides. 2008 Sep;29(9):1603-8. doi: 10.1016/j.peptides.2008.05.003. Epub 2008 May 14.
Obestatin, a novel putative 23-amino acid peptide, was found to be derived from a mammalian preproghrelin gene by using a bioinformatics approach. Although the effects of obestatin on food intake and upper gut motility remain controversial, no studies have been carried out to explore its influence on lower gut motility and secretion. We investigated the impacts of intravenous (IV) injection of obestatin on rat colonic motor and secretory functions. Colonic transit time, fecal pellet output, and fecal content were measured in freely fed, conscious rats, which were chronically implanted with IV and colonic catheters. To test the validity of this animal model, human/rat corticotropin-releasing factor (h/rCRF) served as a stimulatory inducer of colonic motility and secretion. IV injection of obestatin (45, 100, and 300 nmol/kg) did not affect the colonic transit time, whereas IV injection of h/rCRF (30 nmol/kg) effectively accelerated colonic transit time. IV obestatin, in every dose we tested, also did not modify fecal pellet output, frequency of watery diarrhea, total fecal weight, fecal dried solid weight, or fecal fluid weight in the first hour after injection. On the other hand, IV injection of h/rCRF significantly enhanced fecal pellet output, as well as increased the frequency of watery diarrhea, total fecal weight, fecal dried solid weight, and fecal fluid weight during the first hour after injection compared with IV saline controls. In conclusion, peripheral obestatin administration has no impact on colonic motility and secretion in conscious fed rats.
肥胖抑制素是一种推测的新型23个氨基酸的肽，通过生物信息学方法发现它源自哺乳动物的前proghrelin基因。尽管肥胖抑制素对食物摄入和上消化道运动的影响仍存在争议，但尚未开展研究探讨其对下消化道运动和分泌的影响。我们研究了静脉注射肥胖抑制素对大鼠结肠运动和分泌功能的影响。在自由进食、清醒的大鼠中测量结肠转运时间、粪便颗粒排出量和粪便含量，这些大鼠长期植入了静脉导管和结肠导管。为了检验该动物模型的有效性，人/大鼠促肾上腺皮质激素释放因子（h/rCRF）用作结肠运动和分泌的刺激诱导剂。静脉注射肥胖抑制素（45、100和300 nmol/kg）不影响结肠转运时间，而静脉注射h/rCRF（30 nmol/kg）有效加速了结肠转运时间。我们测试的每一个剂量的静脉注射肥胖抑制素在注射后第一小时也未改变粪便颗粒排出量、水样腹泻频率、粪便总重量、粪便干重或粪便液体重量。另一方面，与静脉注射生理盐水对照组相比，静脉注射h/rCRF在注射后第一小时显著增加了粪便颗粒排出量，同时增加了水样腹泻频率、粪便总重量、粪便干重和粪便液体重量。总之，外周给予肥胖抑制素对清醒进食大鼠的结肠运动和分泌没有影响。
