Regulation of eNOS Expression in Brain Endothelial Cells by Perinuclear EP <sub>3</sub> Receptors

  • Fernand Gobeil
    From the Departments of Pediatrics, Ophthalmology, and Pharmacology (F.G., I.D., A.M.M., A.V.-T., S.G.B., D.A., X.H., M.H.B., C.Q., A.B., M.B., S.C.), Research Center of Hôpital Sainte-Justine, Montréal; the Faculty of Biological Sciences (I.D., S.M.), Université de Montréal; the Department of Pharmacology and Therapeutics (A.M.M., M.B., A.R.-d.-S., D.R.V., S.C.), McGill University, Montréal, Québec, Canada; and the Department of Cellular Biology (S.C., G.B.), Université de Sherbrooke,...
  • Isabelle Dumont
    From the Departments of Pediatrics, Ophthalmology, and Pharmacology (F.G., I.D., A.M.M., A.V.-T., S.G.B., D.A., X.H., M.H.B., C.Q., A.B., M.B., S.C.), Research Center of Hôpital Sainte-Justine, Montréal; the Faculty of Biological Sciences (I.D., S.M.), Université de Montréal; the Department of Pharmacology and Therapeutics (A.M.M., M.B., A.R.-d.-S., D.R.V., S.C.), McGill University, Montréal, Québec, Canada; and the Department of Cellular Biology (S.C., G.B.), Université de Sherbrooke,...
  • Anne Marilise Marrache
    From the Departments of Pediatrics, Ophthalmology, and Pharmacology (F.G., I.D., A.M.M., A.V.-T., S.G.B., D.A., X.H., M.H.B., C.Q., A.B., M.B., S.C.), Research Center of Hôpital Sainte-Justine, Montréal; the Faculty of Biological Sciences (I.D., S.M.), Université de Montréal; the Department of Pharmacology and Therapeutics (A.M.M., M.B., A.R.-d.-S., D.R.V., S.C.), McGill University, Montréal, Québec, Canada; and the Department of Cellular Biology (S.C., G.B.), Université de Sherbrooke,...
  • Alejandro Vazquez-Tello
    From the Departments of Pediatrics, Ophthalmology, and Pharmacology (F.G., I.D., A.M.M., A.V.-T., S.G.B., D.A., X.H., M.H.B., C.Q., A.B., M.B., S.C.), Research Center of Hôpital Sainte-Justine, Montréal; the Faculty of Biological Sciences (I.D., S.M.), Université de Montréal; the Department of Pharmacology and Therapeutics (A.M.M., M.B., A.R.-d.-S., D.R.V., S.C.), McGill University, Montréal, Québec, Canada; and the Department of Cellular Biology (S.C., G.B.), Université de Sherbrooke,...
  • Sylvie G. Bernier
    From the Departments of Pediatrics, Ophthalmology, and Pharmacology (F.G., I.D., A.M.M., A.V.-T., S.G.B., D.A., X.H., M.H.B., C.Q., A.B., M.B., S.C.), Research Center of Hôpital Sainte-Justine, Montréal; the Faculty of Biological Sciences (I.D., S.M.), Université de Montréal; the Department of Pharmacology and Therapeutics (A.M.M., M.B., A.R.-d.-S., D.R.V., S.C.), McGill University, Montréal, Québec, Canada; and the Department of Cellular Biology (S.C., G.B.), Université de Sherbrooke,...
  • Daniel Abran
    From the Departments of Pediatrics, Ophthalmology, and Pharmacology (F.G., I.D., A.M.M., A.V.-T., S.G.B., D.A., X.H., M.H.B., C.Q., A.B., M.B., S.C.), Research Center of Hôpital Sainte-Justine, Montréal; the Faculty of Biological Sciences (I.D., S.M.), Université de Montréal; the Department of Pharmacology and Therapeutics (A.M.M., M.B., A.R.-d.-S., D.R.V., S.C.), McGill University, Montréal, Québec, Canada; and the Department of Cellular Biology (S.C., G.B.), Université de Sherbrooke,...
  • Xin Hou
    From the Departments of Pediatrics, Ophthalmology, and Pharmacology (F.G., I.D., A.M.M., A.V.-T., S.G.B., D.A., X.H., M.H.B., C.Q., A.B., M.B., S.C.), Research Center of Hôpital Sainte-Justine, Montréal; the Faculty of Biological Sciences (I.D., S.M.), Université de Montréal; the Department of Pharmacology and Therapeutics (A.M.M., M.B., A.R.-d.-S., D.R.V., S.C.), McGill University, Montréal, Québec, Canada; and the Department of Cellular Biology (S.C., G.B.), Université de Sherbrooke,...
  • Martin H. Beauchamp
    From the Departments of Pediatrics, Ophthalmology, and Pharmacology (F.G., I.D., A.M.M., A.V.-T., S.G.B., D.A., X.H., M.H.B., C.Q., A.B., M.B., S.C.), Research Center of Hôpital Sainte-Justine, Montréal; the Faculty of Biological Sciences (I.D., S.M.), Université de Montréal; the Department of Pharmacology and Therapeutics (A.M.M., M.B., A.R.-d.-S., D.R.V., S.C.), McGill University, Montréal, Québec, Canada; and the Department of Cellular Biology (S.C., G.B.), Université de Sherbrooke,...
  • Christiane Quiniou
    From the Departments of Pediatrics, Ophthalmology, and Pharmacology (F.G., I.D., A.M.M., A.V.-T., S.G.B., D.A., X.H., M.H.B., C.Q., A.B., M.B., S.C.), Research Center of Hôpital Sainte-Justine, Montréal; the Faculty of Biological Sciences (I.D., S.M.), Université de Montréal; the Department of Pharmacology and Therapeutics (A.M.M., M.B., A.R.-d.-S., D.R.V., S.C.), McGill University, Montréal, Québec, Canada; and the Department of Cellular Biology (S.C., G.B.), Université de Sherbrooke,...
  • Asmaa Bouayad
    From the Departments of Pediatrics, Ophthalmology, and Pharmacology (F.G., I.D., A.M.M., A.V.-T., S.G.B., D.A., X.H., M.H.B., C.Q., A.B., M.B., S.C.), Research Center of Hôpital Sainte-Justine, Montréal; the Faculty of Biological Sciences (I.D., S.M.), Université de Montréal; the Department of Pharmacology and Therapeutics (A.M.M., M.B., A.R.-d.-S., D.R.V., S.C.), McGill University, Montréal, Québec, Canada; and the Department of Cellular Biology (S.C., G.B.), Université de Sherbrooke,...
  • Sanaa Choufani
    From the Departments of Pediatrics, Ophthalmology, and Pharmacology (F.G., I.D., A.M.M., A.V.-T., S.G.B., D.A., X.H., M.H.B., C.Q., A.B., M.B., S.C.), Research Center of Hôpital Sainte-Justine, Montréal; the Faculty of Biological Sciences (I.D., S.M.), Université de Montréal; the Department of Pharmacology and Therapeutics (A.M.M., M.B., A.R.-d.-S., D.R.V., S.C.), McGill University, Montréal, Québec, Canada; and the Department of Cellular Biology (S.C., G.B.), Université de Sherbrooke,...
  • Mousumi Bhattacharya
    From the Departments of Pediatrics, Ophthalmology, and Pharmacology (F.G., I.D., A.M.M., A.V.-T., S.G.B., D.A., X.H., M.H.B., C.Q., A.B., M.B., S.C.), Research Center of Hôpital Sainte-Justine, Montréal; the Faculty of Biological Sciences (I.D., S.M.), Université de Montréal; the Department of Pharmacology and Therapeutics (A.M.M., M.B., A.R.-d.-S., D.R.V., S.C.), McGill University, Montréal, Québec, Canada; and the Department of Cellular Biology (S.C., G.B.), Université de Sherbrooke,...
  • Stephane Molotchnikoff
    From the Departments of Pediatrics, Ophthalmology, and Pharmacology (F.G., I.D., A.M.M., A.V.-T., S.G.B., D.A., X.H., M.H.B., C.Q., A.B., M.B., S.C.), Research Center of Hôpital Sainte-Justine, Montréal; the Faculty of Biological Sciences (I.D., S.M.), Université de Montréal; the Department of Pharmacology and Therapeutics (A.M.M., M.B., A.R.-d.-S., D.R.V., S.C.), McGill University, Montréal, Québec, Canada; and the Department of Cellular Biology (S.C., G.B.), Université de Sherbrooke,...
  • Alfredo Ribeiro-da-Silva
    From the Departments of Pediatrics, Ophthalmology, and Pharmacology (F.G., I.D., A.M.M., A.V.-T., S.G.B., D.A., X.H., M.H.B., C.Q., A.B., M.B., S.C.), Research Center of Hôpital Sainte-Justine, Montréal; the Faculty of Biological Sciences (I.D., S.M.), Université de Montréal; the Department of Pharmacology and Therapeutics (A.M.M., M.B., A.R.-d.-S., D.R.V., S.C.), McGill University, Montréal, Québec, Canada; and the Department of Cellular Biology (S.C., G.B.), Université de Sherbrooke,...
  • Daya R. Varma
    From the Departments of Pediatrics, Ophthalmology, and Pharmacology (F.G., I.D., A.M.M., A.V.-T., S.G.B., D.A., X.H., M.H.B., C.Q., A.B., M.B., S.C.), Research Center of Hôpital Sainte-Justine, Montréal; the Faculty of Biological Sciences (I.D., S.M.), Université de Montréal; the Department of Pharmacology and Therapeutics (A.M.M., M.B., A.R.-d.-S., D.R.V., S.C.), McGill University, Montréal, Québec, Canada; and the Department of Cellular Biology (S.C., G.B.), Université de Sherbrooke,...
  • Ghassan Bkaily
    From the Departments of Pediatrics, Ophthalmology, and Pharmacology (F.G., I.D., A.M.M., A.V.-T., S.G.B., D.A., X.H., M.H.B., C.Q., A.B., M.B., S.C.), Research Center of Hôpital Sainte-Justine, Montréal; the Faculty of Biological Sciences (I.D., S.M.), Université de Montréal; the Department of Pharmacology and Therapeutics (A.M.M., M.B., A.R.-d.-S., D.R.V., S.C.), McGill University, Montréal, Québec, Canada; and the Department of Cellular Biology (S.C., G.B.), Université de Sherbrooke,...
  • Sylvain Chemtob
    From the Departments of Pediatrics, Ophthalmology, and Pharmacology (F.G., I.D., A.M.M., A.V.-T., S.G.B., D.A., X.H., M.H.B., C.Q., A.B., M.B., S.C.), Research Center of Hôpital Sainte-Justine, Montréal; the Faculty of Biological Sciences (I.D., S.M.), Université de Montréal; the Department of Pharmacology and Therapeutics (A.M.M., M.B., A.R.-d.-S., D.R.V., S.C.), McGill University, Montréal, Québec, Canada; and the Department of Cellular Biology (S.C., G.B.), Université de Sherbrooke,...

書誌事項

公開日
2002-04-05
DOI
  • 10.1161/01.res.0000013303.17964.7a
公開者
Ovid Technologies (Wolters Kluwer Health)

この論文をさがす

説明

<jats:p> We reported upregulation of endothelial nitric oxide synthase (eNOS) by PGE <jats:sub>2</jats:sub> in tissues and presence of perinuclear PGE <jats:sub>2</jats:sub> receptors (EP). We presently studied mechanisms by which PGE <jats:sub>2</jats:sub> induces eNOS expression in cerebral microvessel endothelial cells (ECs). 16,16-Dimethyl PGE <jats:sub>2</jats:sub> and selective EP <jats:sub>3</jats:sub> receptor agonist M&B28767 increased eNOS expression in ECs and the NO-dependent vasorelaxant responses induced by substance P on cerebral microvessels. These effects could be prevented by prostaglandin transporter blocker bromcresol green and actinomycin D. EP <jats:sub>3</jats:sub> immunoreactivity was confirmed on plasma and perinuclear membrane of ECs. M&B28767 increased eNOS RNA expression in EC nuclei, and this effect was augmented by overexpression of EP <jats:sub>3</jats:sub> receptors. M&B28767 also induced increased phosphorylation of Erk-1/2 and Akt, as well as changes in membrane potential revealed by the potentiometric fluorescent dye RH421, which were prevented by iberiotoxin; perinuclear K <jats:sub>Ca</jats:sub> channels were detected, and their functionality corroborated by NS1619-induced Ca <jats:sup>2+</jats:sup> signals and nuclear membrane potential changes. Moreover, pertussis toxin, Ca <jats:sup>2+</jats:sup> chelator, and channel blockers EGTA, BAPTA, and SK&F96365, as well as K <jats:sub>Ca</jats:sub> channel blocker iberiotoxin, protein-kinase inhibitors wortmannin and PD 98059, and NF-κB inhibitor pyrrolidine dithiocarbamate prevented M&B28767-induced increase in Ca <jats:sup>2+</jats:sup> transients and/or eNOS expression in EC nuclei. We describe for the first time that PGE <jats:sub>2</jats:sub> through its access into cell by prostaglandin transporters induces eNOS expression by activating perinuclear EP <jats:sub>3</jats:sub> receptors coupled to pertussis toxin-sensitive G proteins, a process that depends on nuclear envelope K <jats:sub>Ca</jats:sub> channels, protein kinases, and NF-κB; the roles for nuclear EP <jats:sub>3</jats:sub> receptors seem different from those on plasma membrane. </jats:p>

収録刊行物

  • Circulation Research

    Circulation Research 90 (6), 682-689, 2002-04-05

    Ovid Technologies (Wolters Kluwer Health)

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