Cloning, characterization, and distribution of a mu-opioid receptor in rat brain.

We report the isolation and characterization of a rat cDNA clone encoding a mu-opioid receptor. This receptor, a 398 amino acid protein, shares 59% overall identity with the mouse delta- and kappa-opioid receptors. Transient expression of the receptor in COS cells revealed high-affinity binding of mu-selective opioid antagonists and agonists, with a KD for naloxone approximately 1.5 nM, and for [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and morphine at the high-affinity site of 2-4 nM, confirming a mu-opioid pharmacological profile. Northern blotting and in situ hybridization histochemistry revealed that the mu-opioid receptor mRNA was expressed in many brain regions, including cerebral cortex, caudate putamen, nucleus accumbens, olfactory tubercle, septal nuclei, thalamus, hippocampus, and medial habenular nucleus, in keeping with the known distribution of the mu-opioid receptor.