• DOI:10.1038/377532A0
• Corpus ID: 4326860

Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor

@article{Meunier1995IsolationAS,
  title={Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor},
  author={Jean Claude Meunier and Catherine Mollereau and Lawrence Toll and Charles Suaudeau and Christiane Moisand and Paul Alvinerie and J. L. Butour and Jean Claude Guillemot and Pascual Ferrara and Bernard Monsarrat and Honoré Mazarguil and Gilbert Vassart and Marc Parmentier and Jean Costentin},
  journal={Nature},
  year={1995},
  volume={377},
  pages={532-535}
}

• J. Meunier, C. Mollereau, +11 authors J. Costentin
• Published 12 October 1995
• Biology, Chemistry
• Nature

THE ORL1 receptor, an orphan receptor whose human1and murine2á¤-8 complementary DNAs have recently been characterized, structurally resembles opioid receptors and is negatively coupled with adenylate cyclase1. ORL1 transcripts are particularly abundant in the central nervous system. Here we report the isolation, on the basis of its ability to inhibit the cyclase in a stable recombinant CHO(ORL1 +) cell line, of a neuropeptide that resembles dynorphin A9 and whose amino acid sequence is Phe-Gly-Gly-Phe-Thr-Gly-Ala-Arg-Lys-Ser-Ala-Arg-Lys-Leu-Ala-Asn-Gln. A rat-brain cDNA encodes the peptide flanked by Lys-Arg proteolytic cleavage motifs. The synthetic heptadecapeptide potently inhibits adenylate cyclase in CHO(ORL1 +) cells in culture and induces hyperalgesia when administered intracerebroventricularly to mice. Taken together, these data indicate that the newly discovered heptadecapeptide is an endogenous agonist of the ORL1 receptor and that it may be endowed with pro-nociceptive properties.