Premium
ORL1, a novel member of the opioid receptor family
Author(s) -
Mollereau Catherine,
Parmentier Marc,
Mailleux Pierre,
Butour Jean-Luc,
Moisand Christiane,
Chalon Pascale,
Caput Daniel,
Vassart Gilbert,
Meunier Jean-Claude
Publication year - 1994
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)80235-1
Subject(s) - nociceptin receptor , etorphine , receptor , δ opioid receptor , opioid receptor , adenylyl cyclase , g protein coupled receptor , somatostatin receptor 3 , 5 ht5a receptor , biology , κ opioid receptor , opioid , opioid peptide , somatostatin receptor , microbiology and biotechnology , genetics , (+) naloxone , somatostatin receptor 2
Selective PCR amplification of human and mouse genomic DNAs with oligonucleotides encoding highly conserved regions of the δ‐opioid and somatostatin receptors generated a human DNA probe (hOP01, 761 bp) and its murine counterpart (mOP86, 447 bp). hOP01 was used to screen a cDNA library from human brainstem. A clone (named hORL1) was isolated, sequenced and found to encode a protein of 370 amino acids whose primary structure displays the seven putative membrane‐spanning domains of a G protein‐coupled membrane receptor. The hORL1 receptor is most closely related to opioid receptors not only on structural (sequence) but also on functional grounds: hORLl is 49–50% identical to the murine μ‐, δ‐ and κ ‐opioid receptors and, in CHO‐K1 cells stably transfected with a pRc/CMV:hORLl construct, ORL1 mediates inhibition of adenylyl cyclase by etorphine, a ‘universal’ (nonselective) opiate agonist. Yet, hORLl appears not to be a typical opioid receptor. Neither is it a somatostatin or σ ( N ‐allylnormetazocine) receptor. mRNAs hybridizing with synthetic oligonucleotides complementary to mOP86 are present in many regions of the mouse brain and spinal cord, particularly in limbic (amygdala, hippocampus, septum, habenula,⋯) and hypothalamic structures. We conclude that the hORL1 receptor is a new member of the opioid receptor family with a potential role in modulating a number of brain functions, including instinctive behaviours and emotions.