Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Calcimycin / pharmacology
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Calcineurin
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Calmodulin-Binding Proteins / antagonists & inhibitors
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Calmodulin-Binding Proteins / physiology*
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Kidney Cortex / enzymology*
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Kidney Tubules, Proximal / enzymology*
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Kinetics
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Models, Biological
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Oxymetazoline / pharmacology*
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Peptides / chemistry
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Peptides / pharmacology*
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Phosphoprotein Phosphatases / antagonists & inhibitors
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Phosphoprotein Phosphatases / physiology*
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Polyenes / pharmacology
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Prazosin / pharmacology*
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Rats
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Receptors, Adrenergic, alpha / drug effects
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Receptors, Adrenergic, alpha / physiology*
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Signal Transduction
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Sirolimus
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Sodium-Potassium-Exchanging ATPase / metabolism*
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Tacrolimus / pharmacology
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Yohimbine / pharmacology*
Substances
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Calmodulin-Binding Proteins
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Peptides
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Polyenes
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Receptors, Adrenergic, alpha
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Yohimbine
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Calcimycin
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Oxymetazoline
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Calcineurin
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Phosphoprotein Phosphatases
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Sodium-Potassium-Exchanging ATPase
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Sirolimus
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Tacrolimus
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Prazosin