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Article

Arachidonic Acid Evokes an Increase in Intracellular Ca2+ Concentration and Nitric Oxide Production in Endothelial Cells from Human Brain Microcirculation

1
Biomedicine School, Benemerita Universidad Autonoma de Puebla, 72000 Puebla, Mexico
2
Laboratory of General Physiology, Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, Italy
3
Research Center, Salahaddin University, Erbil 44001, Iraq
4
Department of Life Sciences and Systems Biology, University of Torino, 10123 Torino, Italy
5
Department of Surgical Sciences, University of Torino, 10126 Torino, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this manuscript.
Cells 2019, 8(7), 689; https://doi.org/10.3390/cells8070689
Received: 21 June 2019 / Revised: 4 July 2019 / Accepted: 8 July 2019 / Published: 9 July 2019
(This article belongs to the Special Issue Phospholipids: Dynamic Lipid Signaling in Health and Diseases)
It has long been known that the conditionally essential polyunsaturated arachidonic acid (AA) regulates cerebral blood flow (CBF) through its metabolites prostaglandin E2 and epoxyeicosatrienoic acid, which act on vascular smooth muscle cells and pericytes to vasorelax cerebral microvessels. However, AA may also elicit endothelial nitric oxide (NO) release through an increase in intracellular Ca2+ concentration ([Ca2+]i). Herein, we adopted Ca2+ and NO imaging, combined with immunoblotting, to assess whether AA induces intracellular Ca2+ signals and NO release in the human brain microvascular endothelial cell line hCMEC/D3. AA caused a dose-dependent increase in [Ca2+]i that was mimicked by the not-metabolizable analogue, eicosatetraynoic acid. The Ca2+ response to AA was patterned by endoplasmic reticulum Ca2+ release through type 3 inositol-1,4,5-trisphosphate receptors, lysosomal Ca2+ mobilization through two-pore channels 1 and 2 (TPC1-2), and extracellular Ca2+ influx through transient receptor potential vanilloid 4 (TRPV4). In addition, AA-evoked Ca2+ signals resulted in robust NO release, but this signal was considerably delayed as compared to the accompanying Ca2+ wave and was essentially mediated by TPC1-2 and TRPV4. Overall, these data provide the first evidence that AA elicits Ca2+-dependent NO release from a human cerebrovascular endothelial cell line, but they seemingly rule out the possibility that this NO signal could acutely modulate neurovascular coupling. View Full-Text
Keywords: arachidonic acid; brain microvascular endothelial cells; neurovascular coupling; cerebral blood flow; Ca2+ signalling; nitric oxide; inositol-1,4,5-trisphosphate receptors; two-pore channels 1-2; transient receptor potential vanilloid 4 arachidonic acid; brain microvascular endothelial cells; neurovascular coupling; cerebral blood flow; Ca2+ signalling; nitric oxide; inositol-1,4,5-trisphosphate receptors; two-pore channels 1-2; transient receptor potential vanilloid 4
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MDPI and ACS Style

Berra-Romani, R.; Faris, P.; Negri, S.; Botta, L.; Genova, T.; Moccia, F. Arachidonic Acid Evokes an Increase in Intracellular Ca2+ Concentration and Nitric Oxide Production in Endothelial Cells from Human Brain Microcirculation. Cells 2019, 8, 689. https://doi.org/10.3390/cells8070689

AMA Style

Berra-Romani R, Faris P, Negri S, Botta L, Genova T, Moccia F. Arachidonic Acid Evokes an Increase in Intracellular Ca2+ Concentration and Nitric Oxide Production in Endothelial Cells from Human Brain Microcirculation. Cells. 2019; 8(7):689. https://doi.org/10.3390/cells8070689

Chicago/Turabian Style

Berra-Romani, Roberto, Pawan Faris, Sharon Negri, Laura Botta, Tullio Genova, and Francesco Moccia. 2019. "Arachidonic Acid Evokes an Increase in Intracellular Ca2+ Concentration and Nitric Oxide Production in Endothelial Cells from Human Brain Microcirculation" Cells 8, no. 7: 689. https://doi.org/10.3390/cells8070689

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