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PDE5 says NO to cGMP

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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... As expected, NO-induced PDE5 phosphorylation required cGMP increases and the cGMP-dependent kinase cGKI... Yet phosphorylation was not necessary for PDE5 activation by cGMP, as shown using cGKI-deficient mice... Others recently showed that cGMP binds to and activates PDE5... This interaction probably provides the direct mechanism for NO-induced PDE5 activation... Low concentrations of cGMP, however, stimulated only phosphorylated PDE5, suggesting that the modification may increase cGMP affinity... A small, transient NO stimulus dampened subsequent cGMP production in response to NO ≤1 h later, at which time PDE5 was still active... Inhibition of this active PDE5 may be necessary to achieve lasting nitrovasodilator therapy. ▪

No MeSH data available.


PDE5 activation by cGMP does not require, but is enhanced by, phosphorylation (open circles).
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uro1: PDE5 activation by cGMP does not require, but is enhanced by, phosphorylation (open circles).


PDE5 says NO to cGMP
PDE5 activation by cGMP does not require, but is enhanced by, phosphorylation (open circles).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2255589&req=5

uro1: PDE5 activation by cGMP does not require, but is enhanced by, phosphorylation (open circles).

View Article: PubMed Central

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

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... As expected, NO-induced PDE5 phosphorylation required cGMP increases and the cGMP-dependent kinase cGKI... Yet phosphorylation was not necessary for PDE5 activation by cGMP, as shown using cGKI-deficient mice... Others recently showed that cGMP binds to and activates PDE5... This interaction probably provides the direct mechanism for NO-induced PDE5 activation... Low concentrations of cGMP, however, stimulated only phosphorylated PDE5, suggesting that the modification may increase cGMP affinity... A small, transient NO stimulus dampened subsequent cGMP production in response to NO ≤1 h later, at which time PDE5 was still active... Inhibition of this active PDE5 may be necessary to achieve lasting nitrovasodilator therapy. ▪

No MeSH data available.