Regulation of noncapacitative calcium entry by arachidonic acid and nitric oxide in endothelial cells

Abstract

Several peptides, including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), activate the release of arachidonic acid (AA) and nitric oxide (NO) in endothelial cells (ECs). Both messengers are involved in EC proliferation and vascular permeability and control calcium homeostasis in different ways. Interestingly, it has been recently suggested that NO acts as a downstream mediator of AA-induced calcium entry in smooth muscle cells and isolated mouse parotid cells. In this paper, we have investigated the complex relationships that link intracellular calcium, AA, and NO in cultured endothelial cells. Using different experimental approaches, mainly simultaneous Ca2+ and NO fluorimetric confocal imaging, we provide evidence for a complex pathway leading to noncapacitative calcium entry (NCCE) in bovine aortic endothelial cells (BAECs). In particular, AA is able to induce NCCE through two different pathways: one dependent on eNOS recruitment and NO release, the other NO-independent. Finally, we show that NO increase is involved in the control of BAEC proliferation.

Multiple Roles of Protein Kinase A in Arachidonic Acid–Mediated Ca2+ Entry and Tumor-Derived Human Endothelial Cell Migration

“…Such hypothesis is in agreement with several previous observations on the properties of distinct AA-and NO-operated calcium channels in ECs (6,28). Here, the picture seems particularly complex.…”

“…Several groups, including ours, reported the ability of NO to open calcium channels in the plasma membrane of ECs (6,28). For these reasons, we investigated the effects of NO on Ca c signaling in B-TECs.…”

“…In this context, we previously reported a crosstalk between arachidonateactivated calcium signals and NO metabolism (6). Both AA and NO actually induce a NSOCE in BAECs (1, 2, 5-7); in the same cells, AA promotes NO release even in the absence of calcium entry, giving rise to a complex signaling pathway for NSOCE regulation (6).…”

“…Furthermore, NO, through cyclic guanosine 3′,5′-monophosphate (cGMP)-dependent and cGMP-independent pathways, is able to regulate different types of calciumpermeable channels in ECs (1,2,4,(13)(14)(15)(16)(17)(18)(19)(20). In this context, we previously reported a crosstalk between arachidonateactivated calcium signals and NO metabolism (6). Both AA and NO actually induce a NSOCE in BAECs (1, 2, 5-7); in the same cells, AA promotes NO release even in the absence of calcium entry, giving rise to a complex signaling pathway for NSOCE regulation (6).…”

“…In particular, we previously reported the ability of AA to trigger a NSOCE in bovine aortic ECs (BAEC), playing a critical role in the control of proliferation (1,2,(5)(6)(7).…”