Potential Blood Platelet Target Unraveled for Drug Development Applications

A receptor found on blood platelets whose significance as a potential pharmaceutical target that has long been in doubt may in fact be effective in drug testing research.

Scientists, led by Dana Spence from Michigan State University’s (MSU; East Lansing, USA) department of chemistry, have revealed a way to isolate and test the receptor known as P2X1. By devising a new, simple way to examine it after blood is drawn, the investigators have unveiled 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 in not only developing new pharmaceutic agents but also reevaluating existing medications that could work now by attaching to the receptor. “Scientists are always looking for new ‘druggable’ receptors in the human body,” Dr. 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 was published in the January 6, 2012, issue of the journal Analytical Methods, a journal from the Royal Society of Chemistry (London, UK). The key job of platelets is to help prevent bleeding by way clotting, according to Dr. Spence. They work by getting sticky in the bloodstream, but the difficulty with some disorders such as diabetes or sickle cell anemia is that the platelets get sticky even when they should not, preventing appropriate blood flow and blocking vessels.

Platelets are activated when their receptors are “turned on,” researchers have always focused on the P2Y receptor, which is easily studied. Conversely, the P2X1 receptor was not thought to play a major role in platelet activation, and it was shown very problematic to study because it became desensitized once blood is drawn from the body, according to Dr. Spence.

Even though the scientists tried a couple of approaches to get around that problem--by utilizing different additives or enzymes--the findings did not prove effective in evaluating the receptor. What Dr. Spence and his team discovered is that by adding a simple molecule called NF449--originally believed 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 concluded. “This research opens up new avenues of study and will allow researchers and pharmaceutical companies to reappraise this receptor as a druggable target.”

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