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See Latest ArticlesFunctional characterization of human variants of the mu-opioid receptor gene
Proceedings of the National Academy of Sciences of the United States of America, 07/02/09
Ravindranathan A et al. – Data suggest that S42T, C192F, and S147C variants and other such variants may have clinical relevance to opioid responsiveness to both endogenous ligands and exogenous drugs, and may influence a broad range of phenotypes, including alcohol and substance use disorders (ASUD), pain responses, and development of tolerance to morphine.
Methods- For several naturally occurring amino acid changing variants of the human mu-opioid receptor (MOR), study of the functional consequences of these previously undescribed variants in stably expressing cell lines
- In response to morphine, significant internalization for an L85I variant vs no internalization for WT MOR
- On L85I and WT receptor coexpression, WT MOR internalized with L85I MOR, suggesting dominant L85I phenotype in a heterozygous condition
- Finding potentially important as receptor internalization is associated with development of tolerance to opiate analgesics
- An R181C variant abolished both signaling and internalization in response to saturating doses of the hydrolysis-resistant enkephalin [D-Ala2,N-MePhe4,Gly5-ol]enkephalin (DAMGO)
- R181C and WT receptor coexpression led to independent trafficking of the 2 receptors
- S42T and C192F variants: rightward shift in potency of both morphine and DAMGO
- S147C variant: subtle leftward shift in morphine potency
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