ORL1, a novel member of the opioid receptor family: Cloning, functional expression and localization
Abstract
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.
- Publication:
-
FEBS Letters
- Pub Date:
- January 1994
- DOI:
- 10.1016/0014-5793(94)80235-1
- Bibcode:
- 1994FEBSL.341...33M
- Keywords:
-
- G protein-coupled membrane receptor;
- Etorphine;
- Diprenorphine;
- Cyclic AMP;
- Hybridization;
- in situ;
- Brain;
- Spinal cord;
- CNS;
- central nervous system;
- G protein;
- guanine nucleotide-binding regulatory protein;
- GPCR;
- G protein-coupled membrane receptor;
- ORL1;
- opioid receptor-like receptor or cDNA;
- TMS;
- trans-membrane segment.