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Differential sensitivities of the prostacyclin and nitric oxide biosynthetic pathways to cytosolic calcium in bovine aortic endothelial cells
Author(s) -
Parsaee Heydar,
McEwan Jean R.,
Joseph Sunil,
MacDermot John
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb13400.x
Subject(s) - ionomycin , bradykinin , prostacyclin , isoprenaline , forskolin , chemistry , medicine , endocrinology , endothelium derived relaxing factor , tachyphylaxis , arachidonic acid , in vitro , biochemistry , biology , enzyme , stimulation , receptor
1 Bovine aortic endothelial cells were cultured in vitro , and shown to release both prostacyclin (PGI 2 ; K act = 24.1 n m ) and endothelium‐derived relaxing factor (EDRF, NO; K act = 0.7 n m ) in a concentration‐dependent manner when exposed to bradykinin. 2 The bradykinin‐dependent release of PGI 2 (but not EDRF) was inhibited by 1 μ m isoprenaline or 5 μ m forskolin, and the inhibitory effect of isoprenaline could be reversed by the β 2 ‐adrenoceptor antagonist, ICI 118551. In contrast, isoprenaline had no capacity to inhibit PGI 2 release stimulated by exogenous arachidonic acid. 3 Exposure of cells to bradykinin increased the cytosolic concentration of Ca 2+ ions ([Ca 2+ ] i ; K act = 4.8 n m ), and the effect was inhibited by both 1 μ m isoprenaline and 5 μ m forskolin. 4 In similar experiments, exposure of cells to ionomycin also increased [Ca 2+ ] i and the values of [Ca 2+ ] 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 PGI 2 biosynthesis and that these corresponded to a [Ca 2+ ] i threshold of 350 n m for PGI 2 release while that for EDRF release was less than 200 n m . 5 These differences in Ca 2+ ion sensitivity explain the selective inhibition of bradykinin‐stimulated PGI 2 biosynthesis (to the exclusion of NO biosynthesis) by isoprenaline or forskolin, both of which attenuate bradykinin‐dependent increases in [Ca 2+ ] i .