Calcineurin mediates alpha-adrenergic stimulation of Na+,K(+)-ATPase activity in renal tubule cells.

DOI Web Site 被引用文献4件
  • A Aperia
    Department of Pediatrics, St. Göran's Children's Hospital, Karolinska Institutet, Stockholm, Sweden.
  • F Ibarra
    Department of Pediatrics, St. Göran's Children's Hospital, Karolinska Institutet, Stockholm, Sweden.
  • L B Svensson
    Department of Pediatrics, St. Göran's Children's Hospital, Karolinska Institutet, Stockholm, Sweden.
  • C Klee
    Department of Pediatrics, St. Göran's Children's Hospital, Karolinska Institutet, Stockholm, Sweden.
  • P Greengard
    Department of Pediatrics, St. Göran's Children's Hospital, Karolinska Institutet, Stockholm, Sweden.

説明

<jats:p>The alpha-adrenergic agonist oxymetazoline increased Na+,K(+)-ATPase activity of single proximal convoluted tubules dissected from rat kidney. Activation of the enzyme by oxymetazoline was prevented by either the alpha 1-adrenergic antagonist prazosin or the alpha 2-adrenergic antagonist yohimbine and was mimicked by the calcium ionophore A23187. The effect of oxymetazoline on Na+,K(+)-ATPase activity was prevented by a specific peptide inhibitor of calcineurin, as well as by FK 506, an immunosuppressant agent known to inhibit calcineurin; these results indicate that the action of oxymetazoline is mediated via activation of calcineurin (a calcium/calmodulin-dependent protein phosphatase). Activation of the Na+,K(+)-ATPase by either oxymetazoline or A23187 was associated with a greater than 2-fold increase in its affinity for Na+. The results provide a biochemical mechanism by which norepinephrine, released from renal nerve terminals, stimulates Na+ retention.</jats:p>

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