NO‐synthase‐/NO‐independent regulation of human and murine platelet soluble guanylyl cyclase activity
Open accessAbstract
Objectives Platelets, specialized adhesive cells, play key roles in normal and pathological hemostasis through their ability to rapidly adhere to subendothelial matrix proteins (adhesion) and to other activated platelets (aggregation), functions which are inhibited by nitric oxide (NO). Platelets have been reported to be regulated not only by exogenous endothelium-derived NO, but also by two isoforms of NO synthase, endothelial (eNOS) and inducible (iNOS), endogenously expressed in platelets. however, data concerning expression, regulation and function of eNOS AND iNOS in platelets remain controversial.Methods and results Using important positive (endothelial cells, stimulated macrophages) and negative (eNOS/iNOS knock-out mouse) controls, as well as human platelets highly purified by a newly developed protocol, we now demonstrate that human and mouse platelets do not contain eNOS/iNOS proteins or mRNA. NOS substrate (L-arginine), NOS inhibitors (L-NAME, L-NMMA), and eNOS/iNOS deficiency did not produce detectable functional effects on human and mouse platelets. von Willebrand factor (VWF)/ristocetin treatment of platelets increased cGMP by NO-independent activation of soluble guanylyl cyclase (sGC) which correlated with Src kinase-dependent phosphorylation of sGC beta(1)-subunit-Tyr(192).Conclusions Human and mouse platelets do not express eNOS/iNOS. VWF/ristocetin-mediated activation of the sGC/cGMP signaling pathway may contribute to feedback platelet inhibition.
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NO is a potent inhibitor of PLT aggregation, acting via activation of soluble guanylyl cyclase in PLTs.
“NO is a potent inhibitor of PLT aggregation, acting via activation of soluble guanylyl cyclase in PLTs (64, 65).”
From Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia (2017) · cites this paper as [65]
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Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia
Kuhn, V., Diederich, L., Keller, T. C. S., Kramer, C. M., Lückstädt, W., Panknin, C., Suvorava, T., Isakson, B. E., Kelm, M., & Cortese-Krott, M. M. (2017) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6954 · Cited by 469 · see citing works
Kapil, V., Khambata, R. S., Jones, D. A., Rathod, K., Primus, C., Massimo, G., Fukuto, J. M., & Ahluwalia, A. (2020) · Pharmacological Reviews · doi:10.1124/pr.120.019240 · Cited by 248 · see citing works
- Authors
- GAMBARYAN, S., KOBSAR, A., HARTMANN, S., BIRSCHMANN, I., KUHLENCORDT, P. J., MÜLLER‐ESTERL, W., LOHMANN, S. M., & WALTER, U.
- Affiliations
- Russian Academy of Sciences (RU)
- University of Würzburg (DE)
- University Hospital Frankfurt (DE)
- Corresponding author
- WALTER, U.
- Venue
- Journal of Thrombosis and Haemostasis
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 6
- Issue
- 8
- Pages
- 1376-1384
- ISSN
- 1538-7836 (ISSN-L)
- OpenAlex
- W2012993505
- Cited by
- 118
- References
- 43
- Citations by year
- 2026: 1 · 2025: 4 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 6 · 2019: 2 · 2018: 7 · 2017: 8 · 2016: 9 · 2015: 13 · 2014: 6 · 2013: 4 · 2012: 11
- FWCI
- 8.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Thrombosis and Haemostasis (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB 688)
- Topics
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- platelets, soluble guanylate cyclase, nitric oxide synthase, endothelial nitric oxide synthase, inducible nitric oxide synthase, von Willebrand factor, ristocetin, cGMP signaling, Src kinase, platelet adhesion, platelet aggregation, hemostasis, L-arginine, L-NAME, L-NMMA
- MeSH terms
- Animals, Blood Platelets, Enzyme Activation, Enzyme Inhibitors, Cyclic GMP, Guanylate Cyclase, Humans, Nitric Oxide, Phosphorylation, Ristocetin, RNA, Messenger, Solubility, von Willebrand Factor, Mice, Knockout, Nitric Oxide Synthase, src-Family Kinases, omega-N-Methylarginine, NG-Nitroarginine Methyl Ester, Mice, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, In Vitro Techniques
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