Us RSC Publishing Members Education Science return false;" onKeyPress="JavaScript:redirect('frmareas','area'); return false;" /> UNEXPECTED EFFECTS OF DRUGBINATIONS 13 January 2008 Medicines that use abination of several drugs can sometimes produce unexpected effects in patients.A team of scientists think they have figured out how that can happen.They have shown for the first time how G protein-coupled receptors (GPCRs) - a family of cell surface receptor proteins that are the target of around half of all drugs - respond differently to signalling molecules or drugs when they couple together.Different GPCRs often pair up with each other as dimers in the body, but most previous research has focused on the properties of lone receptors.To investigate howbination effects arise, the team looked at two molecules that work by activating GPCRs - the painkiller morphine and norepinephrine (NE), a signalling molecule that triggers the body's 'fight or flight' response in stressful situations.And norepinephrine normally bind to and activate their receptors.When cells are exposed to both chemicals together, they respond unexpectedly - morphine's effects persist while those of norepinephrine are suppressed.The receptors for morphine and norepinephrine interact directly.Finding may explain why therapiesbining two drugs have unexpected results Vilardaga et al, Nat.Biol.Attached two fluorophores to different parts of the norepinephrine receptor.The inactive receptor, the two fluorophores are close together and look yellow when illuminated by light.But when the receptor is activated, it changes shape.A result, the fluorophores glow blue because they are further apart and no longer interact.'Using this tool, I was able to visualise the activity of the receptor in a live cell in real time,' Jean-Pierre Vilardaga of Harvard Medical School, Boston, US, told _Chemistry World_.When they exposed pairs of morphine and norepinephrine receptors to both chemicals simultaneously, the team saw that the norepinephrine receptor remained inactive - suggesting that it was somehow being switched off by the neighbouring active morphine receptor.'We found that there is a direct cross-talk between one cell surface receptor and another,' Vilardaga said.DRUG DEVELOPMENT The finding neatly explains why norepinephrine has no effect on cells when they're exposed to it at the same time as morphine.The findings could also be relevant to the treatment of Parkinson's disease, which involves another pair of GPCRs.Jean-Philippe Pin of the Institute of Functional Genomics at the University of Montpellier, France, who also works on GPCRs, said, 'My feeling is that will be general to GPCR dimers and could help the development of drugs that are more specific.Bhattacharya _ _Interesting?The word using the 'tools' menu on the left._et al.Chem.Read more A pre-docking role for microtubules in insulin-stimulated glucose transporter 4 translocation
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