PDE5 says NO to cGMP

Ashort burst of nitric oxide (NO) is remembered by a phosphodiesterase long after NO levels decline, according to results on page 719 by Mullershausen et al. The memory of this enzyme, PDE5, may be responsible for the tolerance that patients develop to nitrovasodilators like nitroglycerin.

Nitrovasodilators are NO- releasing compounds that are used to treat coronary heart disease. NO increases cellular cGMP levels, which lowers blood pressure by both relaxing blood vessels and inhibiting platelet aggregation. But platelets rapidly decrease NO-induced cGMP and thus become desensitized to later NO exposure. Circumstantial evidence suggests that the cGMP is degraded upon phosphorylation of the phosphodiesterase PDE5 by a cGMP-dependent kinase. The new article describes a more direct route of cGMP self-limitation.

As expected, NO-induced PDE5 phosphorylation required cGMP increases and the cGMP-dependent kinase...