Wingate Institute of Neurogastroenterology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 26 Ashfield Street, London, E1 2AJ, UK.
Trends Pharmacol Sci. 2011 Jul;32(7):402-9. doi: 10.1016/j.tips.2011.03.009. Epub 2011 Apr 29.
Understanding relationships between gene complements and physiology is important, especially where major species-dependent differences are apparent. Molecular and functional differences between rodents (rats, mice, guinea pigs) and humans are increasingly reported. Recently, the motilin gene, which encodes a gastrointestinal hormone widely detected in mammals, was found to be absent in rodents where the receptors are pseudogenes; however, actions of motilin in rodents are sometimes observed. Although ghrelin shares common ancestry with motilin, major species-dependent abberations are not reported. The apparently specific absence of functional motilin in rodents is associated with specialised digestive physiology, including loss of ability to vomit; motilin is functional in mammals capable of vomiting. The exception is rabbit, the only other mammal unable to vomit, in which motilin might be conserved to regulate caecotrophy, another specialised digestive process. Motilin illustrates a need for caution when translating animal functions to humans. Nevertheless, motilin receptor agonists are under development as gastroprokinetic drugs.
了解基因组成与生理学之间的关系非常重要，特别是在明显存在主要物种依赖差异的情况下。啮齿动物（大鼠、小鼠、豚鼠）与人类之间的分子和功能差异越来越多地被报道。最近，胃动素基因（编码一种在哺乳动物中广泛检测到的胃肠道激素）被发现不存在于受体为假基因的啮齿动物中；然而，有时会观察到胃动素在啮齿动物中的作用。虽然胃饥饿素与胃动素有共同的祖先，但没有报道主要物种依赖的异常。胃动素在啮齿动物中的明显特异性缺失与专门的消化生理学有关，包括丧失呕吐能力；在能够呕吐的哺乳动物中，胃动素是起作用的。唯一的例外是兔子，兔子是唯一不能呕吐的哺乳动物，胃动素可能在调节盲肠营养中起作用，这是另一种专门的消化过程。胃动素说明了在将动物功能转化为人类功能时需要谨慎。尽管如此，胃动素受体激动剂正在作为胃肠动力药物开发。
