The mu opioid receptor: Molecular and functional aspects

The mu opioid receptor (MOR) is predominantly responsible for the analgesic and euphoric effects of morphine, heroin and other morphine-like drugs. Heroin itself is a prodrug with low affinity to mu opioid receptors. It rapidly penetrates into the brain where it is metabolised into the active drug morphine. There exist several alternative spliced forms of the mu opioid receptor (MOR-A, B, C, D, E etc.) which differ in the amino acid sequence of the C-terminus. In addition, there exist a variety of polymorphisms in the MOR gene some of which have functional consequences: Thus, the Ser268Pro variant shows a dramatically reduced receptor coupling to G-proteins and a reduced development of tolerance. Polymorphisms in the promoter regions of the MOR gene alter the responsiveness of the receptor expression to cytokines by altering the binding of transcription factors (STAT-6, NF-kappa-B). Chronic treatment with agonists causes desensitisization via the phosphorylation of the receptor resulting in the uncoupling from the G-proteins. This is followed by the internalisation and the recycling of the receptors which plays an essential role for receptor resensitization.