Ouabain, a steroid hormone that signals with slow calcium oscillations.

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Aizman O, Uhlen P, Lal M, Brismar H, Aperia A

Ouabain, a steroid hormone that signals with slow calcium oscillations.

Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13420-4. Epub 2001 Oct 30.

PubMed ID

11687608 [ View in PubMed

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Abstract

The plant-derived steroid, digoxin, a specific inhibitor of Na,K-ATPase, has been used for centuries in the treatment of heart disease. Recent studies demonstrate the presence of a digoxin analog, ouabain, in mammalian tissue, but its biological role has not been elucidated. Here, we show in renal epithelial cells that ouabain, in doses causing only partial Na,K-ATPase inhibition, acts as a biological inducer of regular, low-frequency intracellular calcium ([Ca(2+)](i)) oscillations that elicit activation of the transcription factor, NF-kappa B. Partial inhibition of Na,K-ATPase using low extracellular K(+) and depolarization of cells did not have these effects. Incubation of cells in Ca(2+)-free media, inhibition of voltage-gated calcium channels, inositol triphosphate receptor antagonism, and redistribution of actin to a thick layer adjacent to the plasma membrane abolished [Ca(2+)](i) oscillations, indicating that they were caused by a concerted action of inositol triphosphate receptors and capacitative calcium entry via plasma membrane channels. Blockade of ouabain-induced [Ca(2+)](i) oscillations prevented activation of NF-kappa B. The results demonstrate a new mechanism for steroid signaling via plasma membrane receptors and underline a novel role for the steroid hormone, ouabain, as a physiological inducer of [Ca(2+)](i) oscillations involved in transcriptional regulation in mammalian cells.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Digoxin	Sodium/potassium-transporting ATPase subunit alpha-1	Protein	Humans	Yes	Inhibitor	Details