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Abstract：
Motilin (MLN), a 22-amino-acid peptide hormone, is generally present in the mucosa of the upper gastrointestinal (GI) tract, mainly the duodenum of mammals, and it regulates GI motility, especially that related to interdigestive migrating contraction. However, MLN and its receptor are absent in mice and rats, and MLN does not cause any mechanical responses in the rat and mouse GI tracts. The guinea-pig is also a rodent, but expression of the MLN gene in the guinea-pig has been reported. In the present study, two guinea-pig MLNs, FIPIFTYSELRRTQEREQNKGL found in the Ensemble Genome Database (gpMLN-1) and FVPIFTYSELRRTQEREQNKRL reported by Xu et al. (2001) (gpMLN-2), were synthesized, and their biological activities were evaluated in the rabbit duodenum and guinea-pig GI tract in vitro. Both gpMLNs showed contractile activity in longitudinal muscle strips of the rabbit duodenum. The EC50 values of gpMLN-1 and gpMLN-2 were slightly higher than that of human MLN (hMLN), but the maximum contractions were as same as that of hMLN. Treatment with GM109 and hMLN-induced receptor desensitization decreased the contractile activity of both gpMLNs, indicating that the two gpMLN candidates are able to activate the MLN receptor (MLN-R) of the rabbit duodenum. In guinea-pig GI preparations, hMLN and gpMLNs did not show any mechanical responses in circular muscle strips from the gastric antrum or in longitudinal strips of the duodenum, ileum and colon although acetylcholine and 1,1-dimethyl-4-phenylpiperazinium (DMPP) caused definite mechanical responses. The DMPP-induced neural responses in the gastric circular muscle and ileal longitudinal muscles were not modified by gpMLN-1. Even in the gastric and ileal strips with intact mucosa, no mechanical responses were seen with either of the gpMLNs. Furthermore, RT-PCR using various primer sets failed to amplify the gpMLN-2 mRNA. In conclusion, gpMLNs including one that was already reported and the other that was newly found in a database were effective to the rabbit MLN-R, whereas they did not cause any contractions or modification of neural responses in the guinea-pig GI tract, indicating that the MLN system is vestigial and not functional in regulation of GI motility in the guinea-pig as well as in other rodents such as rats and mice.
摘要：
莫蒂林（MLN），一种22个氨基酸的肽激素,通常存在于上消化道（GI）的粘膜中，主要是哺乳动物的十二指肠，它调节胃肠运动，尤其是与消化间迁移收缩有关。然而,MLN及其受体在小鼠和大鼠中缺失,和MLN不会在大鼠和小鼠胃肠道中引起任何机械反应。豚鼠也是一种啮齿动物，但是已经报道了MLN基因在豚鼠中的表达。在本研究中,两个豚鼠MLN，FIPIFTYSELRRTQEREQNKGL发现于集合基因组数据库（gpMLN-1）和Xu等人报告的FVPIFTYSELRRTQEREQNKRL。(2001)(gpMLN-2)，是合成的，并在离体兔十二指肠和豚鼠胃肠道中评价其生物学活性。两种gpMLN都在兔十二指肠的纵向肌条中显示出收缩活动。gpMLN-1和gpMLN-2的EC50值略高于人MLN(hMLN),但最大收缩与hMLN相同。用GM109和hMLN诱导的受体脱敏治疗降低了两种gpMLN的收缩活性，表明两种gpMLN候选物能够激活兔十二指肠的MLN受体(MLN-R)。在豚鼠胃肠道制剂中，hMLN和gpMLNs在胃窦的环形肌条或十二指肠的纵向肌条中没有显示任何机械响应，回肠和结肠，尽管乙酰胆碱和1,1-二甲基-4-苯基哌嗪（DMPP）引起了明确的机械响应。gpMLN-1不会改变DMPP诱导的胃环肌和回肠纵肌的神经反应。即使在粘膜完整的胃和回肠带中，任何一种gpMLN均未观察到机械响应。此外，使用各种引物组的RT-PCR未能扩增gpMLN-2mRNA。总之,gpMLNs包括一个已经报道的和另一个在数据库中新发现的gpMLNs对兔子MLN-R有效，而它们在豚鼠胃肠道中没有引起任何收缩或神经反应的改变，表明MLN系统是残留的，在豚鼠以及其他啮齿动物如大鼠和小鼠中对GI运动的调节不起作用。
