Novel neuropeptides as ligands of orphan G protein-coupled receptors

Curr Pharm Des. 2011;17(25):2626-31. doi: 10.2174/138161211797416110.


Neuropeptides control a wide spectrum of physiological functions. They are central to our understanding of brain functions. They exert their actions by interacting with specific G protein-coupled receptors. We however have not found all the neuropeptides that exist in organisms. The search for novel neuropeptides is thus of great interest as it will lead to a better understanding of brain function and disorders. In this review, we will discuss the historical as well as the current approaches to neuropeptide discovery, with a particular emphasis on the orphan GPCR-based strategies. We will also discuss two novel peptides, neuropeptide S and neuromedin S, as examples of the impact of neuropeptide discovery on our understanding of brain functions. Finally, the challenges facing neuropeptide discovery will be discussed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain / physiology*
  • Brain / physiopathology
  • Brain Diseases / drug therapy
  • Brain Diseases / physiopathology
  • Humans
  • Ligands
  • Neuropeptides / metabolism*
  • Receptors, G-Protein-Coupled / metabolism*


  • Ligands
  • Neuropeptides
  • Receptors, G-Protein-Coupled
  • neuromedin S
  • neuropeptide S, human