Advances in blood clot switch understanding
25 Apr 2012 by Evoluted New Media
Scientists have made a leap forward in understanding how a biochemical switch linked to blood-clotting, strokes and heart disease is switched on.
Researchers led by the University of Leicester – and including a team from Cardiff University – focussed on the receptor P2X1, a protein molecule expressed on blood platelets which are involved in blood clotting.
“We have worked on this receptor for the past 15 years and have shown that it plays an important role in blood clotting as well as regulating the diameter of arteries,” lead researcher Professor Richard Evans told Laboratory News.
[caption id="attachment_27721" align="alignright" width="200" caption="Model of the human P2X1 receptor for ATP, the three subunits that make up the functional receptor are shown in red, white and blue"]
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“The receptor actually acts to help with blood clotting as activation of the receptor leads to calcium influx and membrane depolarisation – blocking it with drugs reduces clotting and thrombus formation.”
The research has focussed on how the P2X1 receptor is ‘turned on’. By biochemical studies and purifying the P2X1 receptor and using an electron microscope, the team have ‘visualised’ the receptor and detected changes in its shape when it is activated, Evans said.
The P2X1 receptor is made of three identical parts, and when it is activated, this leads to the parts twisting against each other. By chemically locking the receptor to stop this twisting, the P2X1 could not be fully activated.
“We have the first realistic insight into how a switch linked to blood-clotting, and therefore connected to strokes and heart attacks, is operated,” said Evans, who is from the Department of Cell Physiology and Pharmacology.
It is hoped the research – published in Proceedings of the National Academy of Sciences – could be used to develops drugs to stop the P2X1 receptor being switched on and help prevent stroke and heart attacks.
The work – funded by the Wellcome Trust and the British Heart Foundation – will now investigate how and where P2X receptor drugs bind to the receptor, which should aid in rational drug design.
