CHARACTERIZATION OF THE MURINE MU-OPIOID RECEPTOR GENE

The analgesic and addictive properties of morphine and other opioid dr ugs are thought to result from their interaction with mu opioid recept ors, Using a delta opioid receptor cDNA as a probe, we have isolated a murine mu opioid receptor cDNA clone (mMOR), Stable expression of mMO R in Chinese hamster ovary cells conferred high binding affinity for m u receptor ligands including morphine and [D-Ala(2),N-methyl-Phe(4),Gl y(5)-ol]-enkephalin and low affinity for delta and kappa preferring li gands, Treatment of these cell lines with morphine and other mu agonis ts inhibited forskolin-induced cAMP accumulation, demonstrating a func tional coupling of mMOR to the inhibition of adenylate cyclase, The pr edicted amino acid sequence of mMOR shares approximate to 55% overall amino acid identity with the delta receptor and approximate to 97% ide ntity with the recently reported rat mu opioid receptor, Expression of the mu receptor in mouse brain as revealed by in situ hybridization p arallels the reported pattern of distribution of mu-selective ligand b inding sites, Chromosomal localization (to mouse chromosome 10) and So uthern analysis are consistent with a single mu opioid receptor gene i n the mouse genome, suggesting that the various pharmacologically dist inct forms of the mu receptor arise from alternative splicing, post-tr anslational events, or from a highly divergent gene(s).