Regulation of arachidonic acid release in vascular endothelium. Ca(2+)-dependent and -independent pathways.
Journal Article (Journal Article)
Ca2+ metabolism and its relationship to arachidonic acid release were studied in cultured pig aortic endothelial cells. When cells were treated with bradykinin, a rapid rise in intracellular Ca2+ concentration ([Ca2+]i) occurred. Arachidonic acid release from cells prelabelled with [3H]arachidonic acid and subjected to flow-through conditions closely followed the changes in [Ca2+]i. Attenuation of the Ca2+ response by chelating extracellular and intracellular Ca2+ or by desensitization of receptors led to comparable attenuation of arachidonate release. Activation of protein kinase C inhibited Ca2+ mobilization in response to bradykinin and stimulated arachidonic acid release. Inhibition of protein kinase C had no effect on bradykinin-stimulated arachidonic acid release, suggesting that protein kinase C does not mediate the bradykinin response. The role of GTP-binding regulatory proteins (G-proteins) in mediating the bradykinin response was also investigated. Bradykinin-stimulated arachidonic acid release was not diminished by preincubation with pertussis toxin. Treatment with the G-protein activator AlF4- resulted in the release of a large pool of arachidonic acid and the formation of lysophospholipids. Combined treatment with AlF4- and bradykinin resulted in a greater than additive effect on arachidonic acid release. In contrast with bradykinin, AlF(4-)-stimulated arachidonic acid release was not dependent on the presence of extracellular Ca2+ or the mobilization of intracellular Ca2+. These results demonstrate Ca(2+)-dependent (bradykinin) and Ca(2+)-independent (AlF4-) pathways of phospholipase A2 activation.
Full Text
Duke Authors
Cited Authors
- Buckley, BJ; Barchowsky, A; Dolor, RJ; Whorton, AR
Published Date
- December 1, 1991
Published In
Volume / Issue
- 280 ( Pt 2) / Pt 2
Start / End Page
- 281 - 287
PubMed ID
- 1747101
Pubmed Central ID
- PMC1130543
International Standard Serial Number (ISSN)
- 0264-6021
Digital Object Identifier (DOI)
- 10.1042/bj2800281
Language
- eng
Conference Location
- England