Snapshot Issue 7 February 2005
Beta-arrestin 2 and pde4
In the 1960s, a team of researchers working for Macfarlan Smith – a world leader in the production of alkaloid opiates – was knocked unconscious after having drunk their morning tea which they had inadvertently stirred with a contaminated rod. Upon inspection, it turned out that the rod had been imbibed with what is now known as etorphine, an opioid analogue of morphine, but so much more potent that it is used to subdue the likes of elephants or rhinos.
It is a revelation to none that opium, from the opium poppy Papaver somniferum, was very popular throughout the 19th century not only to satisfy the whims of artists and the learned but also to soothe pains of all sorts. Morphine, an opioid alkaloid, was isolated from opium in the early 1800s by a German chemist Friedrich Wilhelm Sertürner who named it after Morpheus, the Greek god of dreams, because of its capacity to give a lift to one’s physical and psychological emotions, i.e. its analgesic properties.
The biochemical pathways supporting the analgesic effects of morphine are still poorly understood but, recently, a research team based in Geneva discovered the interplay of two proteins, β-arrestin 2 and phosphodiesterase 4 (PDE4), which seem to be directly involved in its regulation. Morphine quenches pain by stimulating opioid receptors which in turn diminish the release of neurosensory transmitters which trigger off the sensation of pain. Hence morphine’s capacity to alleviate pain.
What the Geneva team found out is that beta-arrestin 2 and PDE4 form a complex which interacts with the synaptic transmission of neurosensory molecules. Indeed, they discovered that if beta-arrestin 2 was non-functional then PDE4 activity was impaired and, surprisingly, this resulted in a stronger inhibition of neurosensory transmission and hence in a greater relief of pain. So in effect, smaller doses of morphine would be a more effective pain reliever. Such a discovery is paramount since high doses of the opioid bring on side effects which, in the long run, can be fatal. Scientists now have the means to tinker with the analgesic pathway so that the effects of morphine are enhanced while its toxicity is kept at bay. A blessing for patients suffering from chronic pain.
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