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Calcium‐calmodulin plays a major role in bradykinin‐induced arachidonic acid release by bovine aortic endothelial cells
Author(s) -
Briand Sandie I.,
Bernier Sylvie G.,
Guillemette Gaétan
Publication year - 1996
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19961201)63:3<292::aid-jcb4>3.0.co;2-s
Subject(s) - arachidonic acid , bradykinin , ionomycin , medicine , phospholipase a2 , endocrinology , bradykinin receptor , calmodulin , phospholipase c , chemistry , calcium , biology , biochemistry , receptor , enzyme
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 3 H‐arachidonic acid, ionomycin and Ca 2+ ‐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 (EC 50 = 1.6 ± 0.7 nM). This increase was rapid, reaching a maximal value of fourfold above basal level in 15 min. In a Ca 2+ ‐free medium, bradykinin was still able to release arachidonic acid but with a lower efficiency. Quinacrine (300 μM), a blocker of PLA 2 , completely inhibited bradykinin‐induced arachidonic acid release. The B 2 bradykinin receptor antagonist HOE‐140 completely inhibited bradykinin‐induced arachidonic acid release. The B 1 ‐selective agonist DesArg 9 ‐bradykinin was inactive and the B 1 ‐selective antagonist [Leu 8 ]DesArg 9 ‐bradykinin had no significant effect on bradykinin‐induced arachidonic acid release. The phospholipase C inhibitor U‐73122 (100 μM) decreased bradykinin‐induced arachidonic acid release. The calmodulin inhibitor W‐7 (50 μM) 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 PLA 2 by bradykinin in BAEC is a direct consequence of phospholipase C activation. Ca 2+ ‐calmodulin appears to be the prominent activator of PLA 2 in this system. © 1996 Wiley‐Liss, Inc.