Ghrelin peptides induced contractions and growth hormone secretagogue receptor expression in the chicken gastrointestinal tract

生长素释放肽诱导鸡胃肠道收缩和生长激素促分泌素受体表达

基本信息

批准号：
16580245
负责人：
KITAZAWA Takio
金额：
$ 2.43万
依托单位：
Rakuno Gakuen University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

Background and aim. Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor (GHS-R), and stimulates food intake and gastrointestinal (GI) motility in mammals. In chickens, on the other hand, ghrelin inhibits food intake. This discrepancy prompted us to investigate whether ghrelin affects gastrointestinal motility in the chicken. Methods, The contractile effect of chicken ghrelin was measured isometrically in muscle strips from different regions of the GI tract suspended in an organ bath. The effect of chicken ghrelin was compared with that of rat or human ghrelin. In addition, mRNA expression of ghrelin and GHS-R was examined by quantitative RT-PCR.Results. Among the ghrelin peptides tested (rat, human and chicken ghrelin), only chicken ghrelin caused contraction of muscle strips from the GI tract. No effect was seen in des-octanoylated chicken ghrelin, suggesting that octanoylation at Ser^3 residue was essential for its activity. The contractile response to chick … More en ghrelin in the crop was not affected by tetrodotoxin (TTX), but that in the proventriculus was decreased by TTX and atropine to the same extent. D-Lys^3-GHRP-6 (a GHS-R antagonist) caused a transient contraction and inhibited the chicken ghrelin-induced contraction without affecting the 50 mM high-K^+-induced contraction. The amplitude of the chicken ghrelin-induced contraction was different among GI regions: highest in the crop and colon (70% of high-K^+-induced contraction), moderate in the esophagus and proventriculus (30%), and weak in the small intestine (10-20%) and the ranking order was consistent with GHS-R mRNA expression in each region (colon > crop = esophagus > proventriculus > duodenum =jejunum > ileum). GHS-R mRNA expression in the muscle preparations of crop and proventriculus without mucosa was 2-4 times higher than that in whole segments of crop and proventriculus, indicating that the GHS-R is mainly expressed in smooth muscle layers including enteric nerves. In contrast to the GHS-R expression, ghrelin mRNA was mainly expressed in the mucosa of proventriculus and duodenum.Conclusion. These results indicate that ghrelin stimulates GI contractility and preferentially affects the motor activity of esophagus, crop and colon through myogenic and/or neurogenic mechanisms. These actions are mediated through the GHS-R, which is highly sensitive to chicken ghrelin Less

背景和目的。生长激素释放肽是生长激素促分泌素受体（GHS-R）的内源性配体，刺激哺乳动物的食物摄入和胃肠道（GI）运动，而在鸡中，生长激素释放肽抑制食物摄入。我们研究生长素释放肽是否影响鸡的胃肠运动。方法，在鸡的肌肉条中等长测量生长素释放肽的收缩作用。将鸡生长素释放肽与大鼠或人生长素释放肽的效果进行比较。此外，通过定量RT-PCR检测生长素释放肽和GHS-R的mRNA表达。测试了生长素释放肽（大鼠、人类和鸡生长素释放肽），只有鸡生长素释放肽引起胃肠道肌肉条收缩，在去辛酰化的鸡中未发现任何影响。 ghrelin，表明 Ser^3 残基的辛酰化对其活性至关重要。作物中 ghrelin 的收缩反应不受河豚毒素 (TTX) 的影响，但腺胃中的收缩反应却被 TTX 和阿托品降低。 D-Lys^3-GHRP-6（一种 GHS-R 拮抗剂）引起短暂收缩并抑制鸡 ghrelin 诱导的收缩，但不影响 50 mm 高 K^+ 诱导的收缩在胃肠道区域之间有所不同：嗉囊和结肠最高（高 K^+ 诱导的收缩的 70%），食道和结肠中度中等。腺胃（30%），小肠较弱（10-20%），且排名顺序与各区域 GHS-R mRNA 表达量一致（结肠 > 嗉囊 = 食管 > 腺胃 > 十二指肠=空肠 > 回肠），嗉囊和腺胃无粘膜的肌肉制剂中 GHS-R mRNA 表达量比嗉囊和腺胃全段高 2-4 倍，表明 GHS-R 主要表达于平滑肌层。与GHS-R表达相反，ghrelin mRNA主要在腺胃和十二指肠粘膜中表达。这些结果表明ghrelin刺激胃肠道。收缩性，并通过肌源性和/或神经源性机制优先影响食道、嗉囊和结肠的运动活动。这些作用是通过 GHS-R 介导的，GHS-R 对鸡生长素释放肽高度敏感。