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

abstract

• 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.

authors

• Li, Zhenyu

published proceedings

• J Biol Chem

altmetric score

• 9

author list (cited authors)

• Marjanovic, J. A., Li, Z., Stojanovic, A., & Du, X.

citation count

• 65

publication date

• November 2005

publisher

• Elsevier  Publisher

keywords

• Animals
• Blood Platelets
• Cells, Cultured
• Chlorides
• Ferric Compounds
• Gene Expression Regulation, Enzymologic
• Guanylate Cyclase
• Humans
• Mice
• Mice, Knockout
• Nitric Oxide
• Nitric Oxide Synthase Type II
• Nitric Oxide Synthase Type III
• Platelet Activation
• Platelet Aggregation
• Receptors, Cytoplasmic And Nuclear
• Signal Transduction
• Soluble Guanylyl Cyclase
• Thrombosis

Digital Object Identifier (DOI)

• 10.1074/jbc.M506518200

start page

• 37430

end page

• 37438

volume

• 280

issue

• 45

URL

• http://dx.doi.org/10.1074/jbc.m506518200