Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity : possible implications for opiate addiction

摘要: Opioid drugs play important roles in the clinical management of pain, as well development and treatment drug abuse. The mu opioid receptor is primary site action for most commonly used opioids, including morphine, heroin, fentanyl, methadone. By sequencing DNA from 113 former heroin addicts methadone maintenance 39 individuals with no history or alcohol abuse dependence, we have identified five different single-nucleotide polymorphisms (SNPs) coding region gene. prevalent SNP a nucleotide substitution at position 118 (A118G), predicting an amino acid change putative N-glycosylation site. This displays allelic frequency approximately 10% our study population. Significant differences allele distribution were observed among ethnic groups studied. variant resulting A118G did not show altered binding affinities peptides alkaloids tested. However, binds β-endorphin, endogenous that activates receptor, three times more tightly than common form receptor. Furthermore, β-endorphin potent agonist-induced activation G protein-coupled potassium channels. These results SNPs gene can alter signal transduction may implications normal physiology, therapeutics, vulnerability to develop protection diverse diseases addictive diseases.