Characterization of the Murine μ Opioid Receptor Gene (∗)

Autor: Kaufman, Daniel L., Keith, Duane E., Anton, Benito, Tian, Jide, Magendzo, Karin, Newman, Douglas, Tran, Tuyet H., Lee, Daniel S., Wen, Cindy, Xia, Yu-Rong, Lusis, Aldons J., Evans, Christopher J.
Zdroj: Journal of Biological Chemistry; June 1995, Vol. 270 Issue: 26 p15877-15883, 7p
Abstrakt: The analgesic and addictive properties of morphine and other opioid drugs are thought to result from their interaction with μ opioid receptors. Using a δ opioid receptor cDNA as a probe, we have isolated a murine μ opioid receptor cDNA clone (mMOR). Stable expression of mMOR in Chinese hamster ovary cells conferred high binding affinity for μ receptor ligands including morphine and [D-Ala2,N-methyl-Phe4,Gly5-ol]-enkephalin and low affinity for δ and κ preferring ligands. Treatment of these cell lines with morphine and other μ agonists inhibited forskolin-induced cAMP accumulation, demonstrating a functional coupling of mMOR to the inhibition of adenylate cyclase. The predicted amino acid sequence of mMOR shares ≈55% overall amino acid identity with the δ receptor and ≈97% identity with the recently reported rat μ opioid receptor. Expression of the μ receptor in mouse brain as revealed by in situhybridization parallels the reported pattern of distribution of μ-selective ligand binding sites. Chromosomal localization (to mouse chromosome 10) and Southern analysis are consistent with a single μ opioid receptor gene in the mouse genome, suggesting that the various pharmacologically distinct forms of the μ receptor arise from alternative splicing, post-translational events, or from a highly divergent gene(s).
Databáze: Supplemental Index