Comparison of the gastroprokinetic effects of ghrelin, GHRP-6 and motilin in rats in vivo and in vitro
Comparison of the gastroprokinetic effects of ghrelin, GHRP-6 and motilin in rats in vivo and in vitro
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DOI：
10.1016/j.ejphar.2005.04.008
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发表时间：
2005-05-16
影响因子：
5
通讯作者：
Peeters, T
中科院分区：
文献类型：
--
作者：
Depoortere, I;De Winter, B;Peeters, T
Ghrelin和Motilin形成了一个新的结构相关的多肽家族。我们比较了Ghrelin受体激动剂Ghrelin、生长激素释放肽6(GHRP-6)和胃动素在体内外对大鼠胃肠推进运动的影响。测定伊文思蓝灌胃后对胃排空和转运的影响。在胃窦和胃底条上观察了胃动素、Ghrelin和GHRP-6对胃窦和胃底运动的影响。结果：Ghrelin和Ghrp-6促进大鼠胃排空和转运，Ghrelin比Ghrp-6更有效，Ghrelin对Ghrelin的量效关系呈钟形，而对GHRP-6的量效关系不明显。在胃底或胃窦条，对FFS的神经反应包括一种开放的松弛，这种松弛被加入一氧化氮合酶(NO)-合酶阻断剂L-NAME逆转为胆碱介导的收缩。刺激后的非收缩是胆碱介导的。在正常情况下，Ghrelin激动剂降低胃底条的开放松弛，增加胃窦和胃底条的胆碱能非收缩，眼底肌条的浓度反应曲线呈钟形，其中Ghrelin在1，2 mM(开启反应)和0.66 mU M(油样反应)和GHRP-6在0.50 mM(开启反应)和0.26 mU M(关闭反应)时最大。在1~0.1mM范围内，胃动素对胆碱能兴奋运动反应无影响。在L存在下，胃动素激动剂对胆碱能兴奋运动反应有影响，胃动素在不同实验条件下对胆碱能兴奋运动反应无影响。逆转录聚合酶链式反应(RT-PCR)证实试剂盒中存在生长激素促分泌素受体1a转录本。结论：Ghrelin和GHRP-6促进胃排空和转运，而胃动素则通过激活肠道神经系统中的胆碱能兴奋通路和迷走神经通路来促进胃排空和转运。(C)2005 Elsevier B.V.保留所有权利。
Ghrelin and motilin form a new family of structurally related peptides. We compared the gastroprokinctic effects of ghrelin, the ghrelin receptor agonist, growth hormone releasing peptide 6 (GHRP-6), and motilin in rats in vivo and in vitro.Methods: Ghrelin, GHRP-6 or motilin (10-150 mu g/kg) were injected i.p. and the effects on gastric emptying and transit were measured after intragastric application of Evans blue. In antral and fundic strips the effect of motilin, ghrelin or GHRP-6 was studied (hiring electrical field stimulation (EFS) in the absence and presence of N-G-nitro-L-arginine methyl ester hydrochloride (L-NAME) (300 mu M),Results: Ghrelin and GHRP-6 but not motilin accelerated gastric emptying and transit in rats, Ghrelin was more potent than GHRP-6 and the dose-response relationship for ghrelin but not for GHRP-6 was bell-shaped. In fundic or antral strips, neural responses to FFS consisted of an on-relaxation that was reversed into a cholinergically mediated contraction by, addition of the nitric oxide (NO)-synthase blocker, L-NAME. The post-stimulus off-contraction was cholinergically mediated. Under normal conditions, the ghrelin agonists reduced the on-relaxations in fundic strips and increased the cholinergic off-contractions in antral and fundic strips, The concentration response curves in muscle strips of the fundus were bell-shaped with maximal effects for ghrelin at 1,2 mu M (on-responses) and 0.66 mu M (oil-responses) and for GHRP-6 at 0.50 mu M (on-responses) and 0.26 mu M (off-responses). No effects were observed with motilin between 1 nM and 0.1 mu M. Studies in the presence of L-NAME confirmed the effect of the ghrelin agonists on cholinergic excititory motor responses, No effects were observed with motilin under the different experimental conditions. The presence of growth hormone secretagogue receptor la transcripts in the strip preparations was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR).Conclusion: Ghrelin and GHRP-6 but not motilin accelerate gastric emptying and transit by activating cholinergic excitatory pathways in the enteric nervous system in addition to the known vagal pathways. (c) 2005 Elsevier B.V. All rights reserved.