Differential sensitivities of the prostacyclin and nitric oxide biosynthetic pathways to cytosolic calcium in bovine aortic endothelial cells

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Abstract

Bovine aortic endothelial cells were cultured in vitro, and shown to release both prostacyclin (PGI2; Kact = 24.1 nm) and endothelium‐derived relaxing factor (EDRF, NO; Kact = 0.7 nm) in a concentration‐dependent manner when exposed to bradykinin. The bradykinin‐dependent release of PGI2 (but not EDRF) was inhibited by 1 μm isoprenaline or 5 μm forskolin, and the inhibitory effect of isoprenaline could be reversed by the β2‐adrenoceptor antagonist, ICI 118551. In contrast, isoprenaline had no capacity to inhibit PGI2 release stimulated by exogenous arachidonic acid. Exposure of cells to bradykinin increased the cytosolic concentration of Ca2+ ions ([Ca2+]i; Kact = 4.8 nm), and the effect was inhibited by both 1 μm isoprenaline and 5 μm forskolin. In similar experiments, exposure of cells to ionomycin also increased [Ca2+]i and the values of [Ca2+]i were calibrated in terms of the ionomycin concentration. In subsequent experiments involving exposure of endothelial cells to selected concentrations of ionomycin, it was possible to show that the biosynthesis of NO was triggered at ionomycin concentrations about one tenth of that required for PGI2 biosynthesis and that these corresponded to a [Ca2+]i threshold of 350 nm for PGI2 release while that for EDRF release was less than 200 nm. These differences in Ca2+ ion sensitivity explain the selective inhibition of bradykinin‐stimulated PGI2 biosynthesis (to the exclusion of NO biosynthesis) by isoprenaline or forskolin, both of which attenuate bradykinin‐dependent increases in [Ca2+]i. 1992 British Pharmacological Society

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Parsaee, H., McEwan, J. R., Joseph, S., & MacDermot, J. (1992). Differential sensitivities of the prostacyclin and nitric oxide biosynthetic pathways to cytosolic calcium in bovine aortic endothelial cells. British Journal of Pharmacology, 107(4), 1013–1019. https://doi.org/10.1111/j.1476-5381.1992.tb13400.x

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