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Selected Publication:
Graier, WF; Groschner, K; Schmidt, K; Kukovetz, WR.
Increases in endothelial cyclic AMP levels amplify agonist-induced formation of endothelium-derived relaxing factor (EDRF).
Biochem J. 1992; 288 ( Pt 2)(6):345-349
Doi: 10.1042/bj2880345
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- Leading authors Med Uni Graz
- Graier Wolfgang
- Co-authors Med Uni Graz
- Groschner Klaus
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- Abstract:
- The interaction between intracellular cyclic AMP and agonist-induced endothelium-derived relaxing factor (EDRF) (NO) formation was investigated in pig aortic endothelial cells. Three potent stimulators of adenylate cyclase, namely forskolin, adenosine and isoprenaline, amplified bradykinin- and ATP-induced biosynthesis and release of EDRF. None of the substances by itself affected basal EDRF formation. The effects of forskolin, adenosine and isoprenaline corresponded to an enhanced agonist-induced rise in intracellular free Ca2+ concentration ([Ca2+]i), were mimicked by the membrane-permeable cyclic AMP analogue dibutyryl cyclic AMP and were antagonized by the protein kinase inhibitor N-[2-(methylamino)ethyl]-5-isoquinolinesulphonamide dihydrochloride (H-8). Our data suggest that cyclic AMP-dependent phosphorylation modulates Ca(2+)-signalling and thus the function of endothelial cells. This mechanism may be of particular physiological importance, since it allows a joint regulation of endothelial functions by tissues factors such as bradykinin, which directly affects [Ca2+]i and agonists which affect intracellular cyclic AMP levels.
- Find related publications in this database (using NLM MeSH Indexing)
- Adenosine - pharmacology
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- Calcimycin - pharmacology
- Calcium - metabolism
- Cells, Cultured -
- Cyclic AMP - metabolism
- Endothelium, Vascular - metabolism
- Ethers, Cyclic - pharmacology
- Forskolin - pharmacology
- Isoproterenol - pharmacology
- Isoquinolines - pharmacology
- Nitric Oxide - metabolism
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- Protein Kinases - pharmacology
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