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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。胃饥饿素是生长激素促分泌受体（GHS-R）的内源性配体，刺激哺乳动物的食物摄入和胃肠运动。另一方面，在鸡体内，胃饥饿素抑制食物摄入。这种差异促使我们研究胃饥饿素是否会影响鸡的胃肠运动。方法：将鸡胃肠不同部位的肌肉条悬挂在器官浴中，等距测量胃促生长素的收缩作用。比较了鸡胃饥饿素与大鼠和人胃饥饿素的作用。定量rt - pcr检测ghrelin和GHS-R mRNA的表达。在测试的胃饥饿素肽（大鼠、人类和鸡的胃饥饿素）中，只有鸡的胃饥饿素能引起胃肠道肌肉条的收缩。在去辛烷酰化的鸡胃饥饿素中没有发现任何影响，这表明Ser^3残基的辛烷酰化对其活性至关重要。河蟹毒素（TTX）对作物的收缩反应没有影响，但TTX和阿托品对作物前室的收缩反应有相同程度的降低。D-Lys^3-GHRP-6（一种GHS-R拮抗剂）引起鸡胃饥饿素诱导的短暂性收缩，但不影响50 mM高k ^+诱导的收缩。鸡胃饥饿素诱导的收缩幅度在胃肠道各区域间存在差异：作物和结肠最大（占高k ^+诱导收缩的70%），食道和前脑室中等（占30%），小肠较弱（占10-20%），各区域GHS-R mRNA表达的顺序与各区域GHS-R mRNA表达的顺序一致（结肠bb0作物=食道>前脑室>十二指肠=空肠>回肠）。GHS-R mRNA在未加黏膜的作物肌肉制剂和前脑室中的表达量是作物全节段和前脑室中的2-4倍，说明GHS-R主要在包括肠神经在内的平滑肌层中表达。与GHS-R的表达相反，胃饥饿素mRNA主要表达于胃前部和十二指肠黏膜。这些结果表明，胃饥饿素刺激胃肠道收缩，并通过肌源性和/或神经源性机制优先影响食管、胃和结肠的运动活动。这些作用是通过GHS-R介导的，GHS-R对鸡胃促生长素（ghrelin Less）高度敏感