A receptor found on blood platelets whose importance as a
potential pharmaceutical target has long been questioned may in fact be
fruitful in drug testing, according to new research from Michigan State
University (MSU) chemists.
A team led by Dana Spence of MSU’s Department of
Chemistry has revealed a way to isolate and test the receptor known as P2X1. By
creating a new, simple method to study it after blood is drawn, the team has
unlocked a potential new drug target for many diseases that impact red blood cells,
such as diabetes, hypertension, and cystic fibrosis.
Researchers can evaluate the receptor not only in
developing new drugs but also re-testing existing medications that could work
now by attaching to the receptor.
“Scientists are always looking for new ‘druggable’
receptors in the human body,” Spence said. “This receptor, P2X1, has
long been viewed as not important in platelets; our studies show that is not
necessarily true. The receptor is very active; you just need to be careful in
working with it.”
The research is published in Analytical Methods.
The main job of platelets is to help prevent bleeding via
clotting, Spence said. They work by getting sticky in the bloodstream, but the
problem with some diseases such as diabetes or sickle-cell anemia is that the
platelets get sticky even when they shouldn’t, preventing proper blood flow and
Platelets are activated when their receptors are
“turned on”; currently, researchers have always focused on the P2Y
receptor, which is easily studied. On the other hand, the P2X1 receptor was not
thought to play a major role in platelet activation, and it proved very
troublesome to study since it became desensitized once blood is drawn from the
body, Spence said.
Though scientists tried a pair of methods to get around
that issue—by using different additives or enzymes—the results did not prove
fruitful in studying the receptor.
What Spence and his team found is that by adding a simple
molecule called NF449—originally thought to block the receptor—they were able
to activate the P2X1 receptor in platelets after a blood draw.
“We have discovered a way to
prepare and handle platelets so that we can study the receptor authentically,”
he said. “This research opens up new avenues of study and will allow
researchers and pharmaceutical companies to re-appraise this receptor as a
Filed Under: Drug Discovery