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Calcium‐dependent nitric oxide synthesis in endothelial cytosol is mediated by calmodulin
Abstract
We investigated whether calmodulin mediates the stimulating effect of Ca 2+ on nitric oxide synthase in the cytosol of porcine aortic endothelial cells. Nitric oxide was quantified by activation of a purified soluble guanylate cyclase. The Ca 2+‐sensitivity of nitric oxide synthase was lost after anion exchange chromatography of the endothelial cytosol and could only be reconstituted by addition of calmodulin or heat‐denatured endothelial cytosol. The Ca 2+‐dependent activation of nitric oxide synthase in the cytosol was inhibited by the calmodulin‐binding peptides/proteins melittin, mastoparan, and calcineurin (IC 50 450, 350 and 60 nM, respectively), but not by the calmodulin antagonist, calmidazolium. In contrast, Ca 2+‐calmodulin‐reconstituted nitric oxide synthase was inhibited with similar potency by melittin and calmidazolium. The results suggest that the Ca 2+‐dependent activation of nitric oxide synthase in endothelial cells is mediated by calmodulin.
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Cites
Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
Palmer, R. M. J., Ferrige, A. G., & Moncada, S. (1987) · Nature · doi:10.1038/327524a0 · Cited by 10,704
Cited by
Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation
Dimmeler, S., Fleming, I., Fisslthaler, B., Hermann, C., Busse, R., & Zeiher, A. M. (1999) · Nature · doi:10.1038/21224 · Cited by 3,591
Self-citationStrategies of antioxidant defense
SIES, H. (1993) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1993.tb18025.x · Cited by 1,976
Mammalian nitric oxide synthases
Stuehr, D. J. (1999) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(99)00016-x · Cited by 996
Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase
Fleming, I., & Busse, R. (2003) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00323.2002 · Cited by 940
Self-citationNitric oxide signalling in cardiovascular health and disease
Farah, C., Michel, L. Y. M., & Balligand, J.-L. (2018) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.224 · Cited by 779
Metadata
- Authors
- Busse, R., & Mülsch, A.
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 1990-06-04
- Volume
- 265
- Issue
- 1-2
- Pages
- 133-136
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2094026979
- Cited by
- 511
- References
- 1
- FWCI
- 20.19
- Type
- journal article
- Language
- en
- Open access
- closed
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
