GMP Both Stimulates and Inhibits Platelet Aggregation

Researchers have found that cyclic guanosine monophosphate (cGMP), which activates a protein kinase (PKG), stimulates platelet aggregation, a finding that contradicts the accepted role of cGMP as a clotting inhibitor. Their finding was reported in the January 10, 2003, issue of Cell.

The investigators, from the University of Illinois (Chicago, USA), found that PKG knockout mice showed impaired platelet responses to von Willebrand factor (vWF) or low doses of thrombin and had prolonged bleeding times. Human platelet aggregation induced by vWF or low-dose thrombin was inhibited by PKG inhibitors but enhanced by cGMP. Furthermore, a cGMP-enhancing agent, sildenafil (Viagra), promoted vWF- or thrombin-induced platelet aggregation.

A theory was proposed to harmonize the old findings that cGMP inhibited clotting with the new results. The authors speculated that cGMP stimulated platelets in a biphasic manner, an initial transient stimulatory response that promoted platelet aggregation and a subsequent inhibitory response that limited the size of the clot to prevent clogging of blood vessels.

The study also highlighted a potential danger in the use of Viagra, which acts to raise levels of cGMP. Individuals with a tendency towards atherosclerosis might be in danger of cardiovascular blockage due to the increased likelihood of platelet aggregation.



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