Characterization of G proteins involved in activation of nonselective cation channels and arachidonic acid release by norepinephrine/alpha1A-adrenergic receptors.

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  • Author(s): Kawanabe Y;Kawanabe Y; Hashimoto N; Masaki T
  • Source:
    American journal of physiology. Cell physiology [Am J Physiol Cell Physiol] 2004 Mar; Vol. 286 (3), pp. C596-600.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901225 Publication Model: Print Cited Medium: Print ISSN: 0363-6143 (Print) Linking ISSN: 03636143 NLM ISO Abbreviation: Am J Physiol Cell Physiol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Bethesda, Md. : American Physiological Society,
    • Subject Terms:
      Adrenergic alpha-Agonists/*pharmacology ; Arachidonic Acid/*metabolism ; Calcium Channels/*metabolism ; GTP-Binding Proteins/*metabolism ; Norepinephrine/*pharmacology ; Receptors, Adrenergic, alpha-1/*metabolism; Adrenergic alpha-1 Receptor Agonists ; Amides/pharmacology ; Androstadienes/pharmacology ; Animals ; CHO Cells ; Cation Transport Proteins/metabolism ; Cricetinae ; Enzyme Inhibitors/pharmacology ; Estrenes/pharmacology ; GTP-Binding Proteins/genetics ; Mutagenesis ; Phosphodiesterase Inhibitors/pharmacology ; Pyridines/pharmacology ; Pyrrolidinones/pharmacology ; Transfection ; Wortmannin
    • Abstract:
      We demonstrated recently that norepinephrine activates Ca2+ -permeable nonselective cation channels (NSCCs) in Chinese hamster ovary cells stably expressing alpha1A-adrenergic receptors (CHO-alpha1A). Moreover, extracellular Ca2+ through NSCCs plays essential roles in norepinephrine-induced arachidonic acid release. The purpose of the present study was to identify the G proteins involved in the activation of NSCCs and arachidonic acid release by norepinephrine. For these purposes, we used U73122, an inhibitor of phospholipase C (PLC), and dominant negative mutants of G12 and G13 (G12G228A and G13G225A, respectively). U73122 failed to inhibit NSCCs activation by norepinephrine. The magnitudes of norepinephrine-induced extracellular Ca2+ influx in CHO-alpha1A microinjected with G13G225A were smaller than those in CHO-alpha1A. In contrast, the magnitudes of norepinephrine-induced extracellular Ca2+ influx in CHO-alpha1A microinjected with G12G228A were similar to those in CHO-alpha1A. In addition, neither a Rho-associated kinase (ROCK) inhibitor nor a phosphoinositide 3-kinase inhibitor affected norepinephrine-induced extracellular Ca2+ influx. G13G225A, but not G12G228A, also inhibited arachidonic acid release partially. These results demonstrate that 1) the Gq/PLC-pathway is not involved in NSCCs activation by norepinephrine, 2) G13 couples with CHO-alpha1A and plays important roles for norepinephrine-induced NSCCs activation, 3) neither ROCK- nor PI3K-dependent cascade is involved in NSCCs activation, and 4) G13 is involved in norepinephrine-induced arachidonic acid release in CHO-alpha1A.
    • Accession Number:
      0 (Adrenergic alpha-1 Receptor Agonists)
      0 (Adrenergic alpha-Agonists)
      0 (Amides)
      0 (Androstadienes)
      0 (Calcium Channels)
      0 (Cation Transport Proteins)
      0 (Enzyme Inhibitors)
      0 (Estrenes)
      0 (Phosphodiesterase Inhibitors)
      0 (Pyridines)
      0 (Pyrrolidinones)
      0 (Receptors, Adrenergic, alpha-1)
      112648-68-7 (1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione)
      138381-45-0 (Y 27632)
      27YG812J1I (Arachidonic Acid)
      EC 3.6.1.- (GTP-Binding Proteins)
      X4W3ENH1CV (Norepinephrine)
      XVA4O219QW (Wortmannin)
    • Publication Date:
      Date Created: 20040206 Date Completed: 20040323 Latest Revision: 20200930
    • Publication Date:
      20240829
    • Accession Number:
      10.1152/ajpcell.00359.2003
    • Accession Number:
      14761886