PT  - JOURNAL ARTICLE
AU  - Y Chen
AU  - A Mestek
AU  - J Liu
AU  - J A Hurley
AU  - L Yu
TI  - Molecular cloning and functional expression of a mu-opioid receptor from rat brain.
DP  - 1993 Jul 01
TA  - Molecular Pharmacology
PG  - 8--12
VI  - 44
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/44/1/8.short
4100  - http://molpharm.aspetjournals.org/content/44/1/8.full
SO  - Mol Pharmacol1993 Jul 01; 44
AB  - Opioid drugs act on specific receptors to modulate a wide range of physiological functions. There are at least three types of opioid receptors, mu, delta, and kappa. Using a cDNA probe for a mouse delta-opioid receptor in low stringency hybridization, a clone has been isolated from a rat brain cDNA library. This clone contains an open reading frame of 1194 base pairs, with a deduced polypeptide of 398 amino acid residues. The predicted protein exhibits the structural features of guanine nucleotide-binding protein-coupled receptors and displays a high degree of sequence homology with the mouse delta-opioid receptor. When transfected into COS-7 cells, the cDNA conferred a binding site with subnanomolar affinity for [3H]diprenorphine, a high affinity ligand for all three types of opioid receptors. This site also displayed nanomolar affinity for [D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAGO), a mu-selective agonist, whereas its affinities for the delta-selective agonist [D-Pen2,5]-enkephalin and the kappa-selective agonist U-50488 were in the micromolar range. Several mu-selective antagonists, including naloxonazine, beta-funaltrexamine, and cyprodime, were capable of displacing [3H]diprenorphine binding with nanomolar potency. The pharmacological profile of this binding site thus suggests that it is a mu-type opioid receptor, which we designated MOR-1. In COS-7 cells expressing MOR-1 and stimulated with forskolin, treatment with DAGO decreased the steady state levels of cAMP; this inhibitory effect of DAGO was blocked by naloxonazine. These results suggest that this mu-opioid receptor is functionally coupled to the inhibition of adenylyl cyclase.