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

背景和目标。生长素释放蛋白是生长本元促分泌受体（GHS-R）的内源配体，并刺激哺乳动物中的食物摄入和胃肠道（GI）运动。另一方面，在鸡中，生长素素会抑制食物摄入量。这种差异促使我们调查生长素素是否影响鸡肉中的胃肠道运动。方法，在悬挂在器官浴中的胃肠道的不同区域的肌肉条中，用等肌条对鸡的收缩效应进行了同位测量。将鸡肉生蛋白的作用与大鼠或人类生长素蛋白的作用进行了比较。另外，通过定量RT-PCR.RESULTS检查了生长素蛋白和GHS-R的mRNA表达。在经过测试的生长素蛋白肽（大鼠，人和鸡肉生蛋白）中，只有鸡肉生肽引起了胃肠道的肌肉条的收缩。在Des-octanoylated鸡长素中未见影响，这表明Ser^3住所的辛酰化对于其活性至关重要。收缩对雏鸡的反应……农作物中更多的生长素蛋白不受四毒素（TTX）的影响，但是在Proventriculus中，TTX改善了Proventriculus，并在同一程度上得到了肤色。 D-Lys^3-GHRP-6（A GHS-R拮抗剂）引起了短暂的收缩，并抑制了鸡肉酶诱导的收缩，而不会影响50 mm High-k^+ - 诱导的收缩。 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）。在没有粘膜的肌肉制剂中，GHS-R mRNA的表达比在农作物和proventriculus的整个部分中的肌肉制剂中的表达高2-4倍，这表明GHS-R主要在包括肠神经在内的平滑肌层中表达。与GHS-R表达相反，Ghrelin mRNA主要在Proventriculus和DuodeNum.Conclusion的粘膜中表达。这些结果表明，生长素蛋白会刺激GI收缩力，并优先通过肌原性和/或神经源性机制影响食道，农作物和结肠的运动活性。这些动作是通过GHS-R介导的，GHS-R对鸡皮蛋白非常敏感