An opioid-like system regulating feeding behavior in C. elegans

Elife. 2015 Apr 21;4:e06683. doi: 10.7554/eLife.06683.

Abstract

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.

Keywords: C. elegans; feeding regulation; neuropeptide; neuroscience; opioid.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Conserved Sequence
  • Feeding Behavior / drug effects
  • Feeding Behavior / physiology*
  • Gene Expression Regulation
  • Molecular Sequence Data
  • Morphine / pharmacology
  • Naloxone / pharmacology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Receptors, Opioid / deficiency
  • Receptors, Opioid / genetics*
  • Signal Transduction
  • Starvation / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Neuropeptides
  • Receptors, Opioid
  • Naloxone
  • Morphine