Rapid nitric oxide-induced desensitization of the cGMP response is caused by increased activity of phosphodiesterase type 5 paralleled by phosphorylation of the enzyme

Citation
F. Mullershausen et al., Rapid nitric oxide-induced desensitization of the cGMP response is caused by increased activity of phosphodiesterase type 5 paralleled by phosphorylation of the enzyme, J CELL BIOL, 155(2), 2001, pp. 271-278
Citations number
25
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
0021-9525 → ACNP
Volume
155
Issue
2
Year of publication
2001
Pages
271 - 278
Database
ISI
SICI code
0021-9525(20011015)155:2<271:RNODOT>2.0.ZU;2-H
Abstract
Most of the effects of the signaling molecule nitric oxide (NO) are mediate d by cGMP, which is synthesized by soluble guanylyl cyclase and degraded by phosphodiesterases. Here we show that in platelets and aortic tissue, NO l ed to a biphasic response characterized by a tremendous increase in cGMP (u p to 100-fold) in less than 30 s and a rapid decline, reflecting the tightl y controlled balance of guanylyl cyclase and phosphodiesterase activities. Inverse to the reported increase in sensitivity caused by NO shortage, conc entrating NO attenuated the cGMP response in a concentration-dependent mann er. We found that guanylyl cyclase remained fully activated during the enti re course of the cGMP response; thus, desensitization was not due to a swit ched off guanylyl cyclase. However, when intact platelets were incubated wi th NO and then lysed, enhanced activity of phosphodiesterase type 5 was det ected in the cytosol. Furthermore, this increase in cGMP degradation is par alleled by the phosphorylation of phosphodiesterase type 5 at Ser-92. Thus, our data suggest that NO-induced desensitization of the cGMP response is c aused by the phosphorylation and subsequent activity increase of phosphodie sterase type 5.