Stimulatory roles of nitric-oxide synthase 3 and guanylyl cyclase in platelet activation

Jasna A. Marjanovic, Zhenyu Li, Aleksandra Stojanovic, Xiaoping Du

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


Nitric oxide (NO) stimulates soluble guanylyl cyclase and, thus, enhances cyclic guanosine monophosphate (cGMP) levels. It is a currently prevailing concept that NO inhibits platelet activation. This concept, however, does not fully explain why platelet agonists stimulate NO production. Here we show that a major platelet NO synthase (NOS) isoform, NOS3, plays a stimulatory role in platelet secretion and aggregation induced by low doses of platelet agonists. Furthermore, we show that NOS3 promotes thrombosis in vivo. The stimulatory role of NOS is mediated by soluble guanylyl cyclase and results from a cGMP-dependent stimulation of platelet granule secretion. These findings delineate a novel signaling pathway in which agonists sequentially activate NOS3, elevate cGMP, and induce platelet secretion and aggregation. Our data also suggest that NO plays a biphasic role in platelet activation, a stimulatory role at low NO concentrations and an inhibitory role at high NO concentrations.

Original languageEnglish
Pages (from-to)37430-37438
Number of pages9
JournalJournal of Biological Chemistry
Issue number45
StatePublished - Nov 11 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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