Calcium influx, arachidonic acid, and control of endothelial cell proliferation

Recent evidences suggest a role for arachidonic acid (AA) in the triggering of store-independent, or non-capacitative, calcium entry in different cell types. Here, using patch clamp and fluorimetric single-cell calcium measurements, we provide evidence for AA-activated calcium influx in bovine aortic endothelial cells (BAEC). AA-activated calcium entry is independent from intracellular calcium stores depletion at low doses of the fatty acid (<5 <mu>M) and insensitive to a decrease of pH to 6.7. The mimicking effect of 5,8,11,14-eicosatetraynoic acid (ETYA), an acetylenic AA analogue which blocks all AA metabolizing enzymes by acting as a false substrate, and the insensitivity to blockers of AA metabolism (indomethacin and norclihydroguaiaretic acid, NDGA), support the hypothesis of a direct effect of AA, excluding a relevant role of its derivatives in this process. Single-channel analysis in inside-out configuration reveals the presence of a family of AA-activated calcium-permeable channels, with different conductances and reversal potentials. Treatment with AA or ETYA induces a proliferative effect, significantly affected by external EGTA application during the early period (up to 2 h) of stimulation with the agonists. We conclude that low concentrations of arachidonic acid are able to evoke a store-independent calcium influx, exerting a mitogenic role in BAECs. (C) 2001 Harcourt Publishers Ltd.