A sticky problem solved

A small cut won’t bleed for long because tiny blood cells called platelets stick together and trigger clots. Damaged blood vessels and red blood cells release a compound known as adenosine diphosphate, or ADP, which triggers the process that makes platelets sticky.

Sometimes, however, overly reactive platelets are attracted to arteries damaged by fatty buildup. There, they form clots that, if dislodged, can sweep into the heart or brain, where they sometimes cause heart attacks or strokes.

Researchers know that two drugs—clopidogrel and ticlopidine—that are used to reduce the risk of heart attack and stroke work by blocking an ADP receptor found on the surface of platelets. However, analyzing the receptor itself has been a sticky problem, says Pamela B. Conley of COR Therapeutics in San Francisco. Researchers want to learn the sequence of amino acids in that protein.

“Knowing the . . . sequence will allow us to design better inhibitors for this receptor [and thus better drugs]”, Conley says. Clopidogrel and ticlopidine are relatively slow-acting because they must be broken down by the liver before they inhibit clotting.

To frog eggs, Conley and her colleagues added a mixture of genetic material isolated from rat platelets. They’d already engineered the eggs, which don’t normally have an ADP receptor, to produce an electrical signal when the ADP receptor is present and binds to ADP. Cells that received the rat ADP-receptor gene produced a detectable electric current, while cells getting other genes did not. Using electrical signals as their cue, the researchers isolated the rat ADP-receptor gene, they report in the Jan. 11 Nature.

“All in all, they make a convincing case that they have indeed identified this biologically and clinically important molecule,” says Skip Brass of the University of Pennsylvania in Philadelphia in an accompanying editorial.