Calcium-calmodulin plays a major role in bradykinin-induced arachidonic acid release by bovine aortic endothelial cells
✍ Scribed by Sandie I. Briand; Sylvie G. Bernier; Gaétan Guillemette
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 912 KB
- Volume
- 63
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
We provided evidence that calcium-calmodulin plays a major role in bradykinin-induced arachidonic acid release by bovine aortic endothelial cells. In cells labeled for 16 hr with 3H-arachidonic acid, ionomycin and Ca2+-mobilizing hormones such as bradykinin, thrombin and platelet activating factor induced arachidonic acid release. However, arachidonic acid release was not induced by agents known to increase cyclic AMP (forskolin, isoproterenol) or cyclic GMP (sodium nitroprusside). Bradykinin induced the release of arachidonic acid in a dose-dependent manner (EC5,, = 1.6 ? 0.7 nM). This increase was rapid, reaching a maximal value of fourfold above basal level in 15 min. In a CaZ+-free medium, bradykinin was still able to release arachidonic acid but with a lower efficiency. Quinacrine (300 pM), a blocker of PLA2, completely inhibited bradykinin-induced arachidonic acid release. The B2 bradykinin re(-eptor antagonist HOE-I 40 completely inhibited bradykinin-induced arachidonic acid release. The B,-selective agonist DesArgq-bradykinin was inactive and the B,-selective antagonist [Leu8]DesArgq-bradykinin had no significant effect on bradykinin-induced arachidonic acid release. The phospholipase C inhibitor U-73122 (100 p,M) decreased bradykinininduced arachidonic acid release. The calmodulin inhibitor W-7 (50 p,M) drastically reduced the bradykinin-and ionomycin-induced arachidonic acid release. Also, forskolin decreased bradykinin-induced arachidonic acid release. These results suggest that the activation of PLA2 by bradykinin in BAEC is a direct consequence of phospholipase C: activation. Ca2+-calmodulin appears to be the prominent activator of PLA2 in this system. o 1996 WiIey-Ltss, inc.