Cheong Mi Cheong, Artyukhin Alexander B, You Young-Jai, Avery Leon
Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, United States.
Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, United States.
Elife. 2015 Apr 21;4:e06683. doi: 10.7554/eLife.06683.
Neuropeptides are essential for the regulation of appetite. Here we show that neuropeptides could regulate feeding in mutants that lack neurotransmission from the motor neurons that stimulate feeding muscles. We identified nlp-24 by an RNAi screen of 115 neuropeptide genes, testing whether they affected growth. NLP-24 peptides have a conserved YGGXX sequence, similar to mammalian opioid neuropeptides. In addition, morphine and naloxone respectively stimulated and inhibited feeding in starved worms, but not in worms lacking NPR-17, which encodes a protein with sequence similarity to opioid receptors. Opioid agonists activated heterologously expressed NPR-17, as did at least one NLP-24 peptide. Worms lacking the ASI neurons, which express npr-17, did not response to naloxone. Thus, we suggest that Caenorhabditis elegans has an endogenous opioid system that acts through NPR-17, and that opioids regulate feeding via ASI neurons. Together, these results suggest C. elegans may be the first genetically tractable invertebrate opioid model.
神经肽对于食欲调节至关重要。在此我们表明，神经肽可在缺乏来自刺激进食肌肉的运动神经元神经传递的突变体中调节进食。我们通过对115个神经肽基因进行RNA干扰筛选鉴定出了nlp - 24，并测试它们是否影响生长。NLP - 24肽具有保守的YGGXX序列，类似于哺乳动物阿片类神经肽。此外，吗啡和纳洛酮分别刺激和抑制饥饿蠕虫的进食，但对缺乏NPR - 17的蠕虫无此作用，NPR - 17编码一种与阿片受体序列相似的蛋白质。阿片类激动剂激活了异源表达的NPR - 17，至少一种NLP - 24肽也有此作用。缺乏表达npr - 17的ASI神经元的蠕虫对纳洛酮无反应。因此，我们认为秀丽隐杆线虫具有一个通过NPR - 17起作用的内源性阿片系统，且阿片类物质通过ASI神经元调节进食。总之，这些结果表明秀丽隐杆线虫可能是首个具有遗传可操作性的无脊椎动物阿片模型。
