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Unmixing the messages

Posted on January 18th, 2016 by in Pharma R&D

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Have you ever driven through a red light because you were looking at the wrong traffic signal? Or had a row of angry motorists behind you because you hadn’t realized the signal above your lane had turned green? Sometimes the amount of signals at a traffic junction just leads to confusion.
Messages in cells are also guided by signals. The strength of these signals can be altered to change the way a chemical affects a cell. Imagine you have to decide whether to turn right or left and there is a room full of people advising you: half are shouting “turn right” and the other half “turn left”. Result? utter confusion. If you manage to silence most of the people shouting “turn left” you will hear and follow the “turn right” advice.
So what is the medicinal advantage of changing the signal strength? An interesting case is the use of morphine in pain relief. It is well known that morphine has many nasty side effects and work on decreasing these effects has proved ineffective. An alternative way of decreasing these side effects is to reduce the messaging that says “this medicine is making you nauseous” and increase the “you no longer feel pain” message. Sounds simple but in a cell there are many different signals which cause these effects. Most medicines non selectively generate multiple signals, with some leading to good effects, and others leading to adverse events. A review in Bioorganic and Medicinal Chemistry Letters looks at the ways G protein coupled receptors (GPCRs), which are active in cell signalling, can be targeted to refine signalling towards desirable effects.
This area of research for new medicines is still in its early stages. The complexity of the effects involved mean that promising in vitro results do not always work in vivo. This is an area which could potentially be beneficial for many medicines whose use is restricted due to their serious side effects. There is a lot of work to be done still but an interesting area for research.

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