title: Regulation of platelet granule exocytosis by S-nitrosylation.
abstract: Nitric oxide (NO) regulates platelet activation by cGMP-dependent mechanisms and by mechanisms that are not completely defined. Platelet activation includes exocytosis of platelet granules, releasing mediators that regulate interactions between platelets, leukocytes, and endothelial cells. Exocytosis is mediated in part by N-ethylmaleimide-sensitive factor (NSF), an ATPase that disassembles complexes of soluble NSF attachment protein receptors. We now demonstrate that NO inhibits exocytosis of dense granules, lysosomal granules, and alpha-granules from human platelets by S-nitrosylation of NSF. Platelets lacking endothelial NO synthase show increased rolling on venules, increased thrombosis in arterioles, and increased exocytosis in vivo. Regulation of exocytosis is thus a mechanism by which NO regulates thrombosis.
authors.affiliation: Department of Comparative Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Craig N
authors.initials: CN
authors.lastname: Morrell
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsushita
authors.forename: Kelly
authors.initials: K
authors.lastname: Chiles
authors.forename: Robert B
authors.initials: RB
authors.lastname: Scharpf
authors.forename: Munekazu
authors.initials: M
authors.lastname: Yamakuchi
authors.forename: Rebecca J A
authors.initials: RJ
authors.lastname: Mason
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bergmeier
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Mankowski
authors.forename: William M
authors.initials: WM
authors.lastname: Baldwin
authors.forename: Nauder
authors.initials: N
authors.lastname: Faraday
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Lowenstein
mesh_terms: D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D006152:Cyclic GMP / Q000502:physiology; D003594:Cytoplasmic Granules / Q000378:metabolism*; D005089:Exocytosis; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology; D052250:Nitric Oxide Synthase Type III; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D033921:Vesicular Transport Proteins / Q000502:physiology
chemical_list: D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D033921:Vesicular Transport Proteins; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP
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