Ouabain potentiates the activation of ERK1/2 by carbachol in parotid gland epithelial cells; inhibition of ERK1/2 reduces Na(+)-K(+)-ATPase activity.

Content Provider	Semantic Scholar
Author	Plourde, Deana Soltoff, Stephen P.
Copyright Year	2006
Abstract	The Na(+)-K(+)-ATPase and the ERK1/2 pathway appear to be linked in some fashion in a variety of cells. The Na(+)-K(+)-ATPase inhibitor ouabain can promote ERK1/2 activation. This activation involves Src, intracellular Ca(2+) concentration ([Ca(2+)](i)) elevation, reactive oxygen species (ROS) generation, and EGF receptor (EGFR) transactivation. In contrast, ERK1/2 can mediate changes in Na(+)-K(+)-ATPase activity and/or expression. Thus signaling between ERK1/2 and Na(+)-K(+)-ATPase can occur from either direction. Whether such bidirectionality can occur within the same cell has not been reported. In the present study, we have demonstrated that while ouabain (1 mM) produces only a small ( approximately 50%) increase in ERK1/2 phosphorylation in freshly isolated rat salivary (parotid acinar) epithelial cells, it potentiates the phosphorylation of ERK1/2 by submaximal concentrations of carbachol, a muscarinic receptor ligand that initiates fluid secretion. Although ERK1/2 is only modestly phosphorylated when cells are exposed to 1 mM ouabain or 10(-6) M carbachol, the combination of these agents promotes ERK1/2 phosphorylation to near-maximal levels achieved by a log order carbachol concentration. These effects of ouabain are distinct from Na(+)-K(+)-ATPase inhibition by lowering extracellular K(+), which promotes a rapid and large increase in ERK1/2 phosphorylation. ERK1/2 potentiation by ouabain (EC(50) approximately 100 muM) involves PKC, Src, and alterations in [Ca(2+)](i) but not ROS generation or EGFR transactivation. In addition, inhibition of ERK1/2 reduces Na(+)-K(+)-ATPase activity (measured as stimulation of Qo(2) by carbachol and the cationophore nystatin). These results suggest that ERK1/2 and Na(+)-K(+)-ATPase may signal to each other in each direction under defined conditions in a single cell type.
Starting Page	77
Ending Page	91
Page Count	15
File Format	PDF HTM / HTML
DOI	10.1152/ajpcell.00213.2005
PubMed reference number	16236826
Journal	Medline
Volume Number	290
Issue Number	3
Alternate Webpage(s)	http://ajpcell.physiology.org/content/ajpcell/290/3/C702.full.pdf
Alternate Webpage(s)	https://doi.org/10.1152/ajpcell.00213.2005
Journal	American journal of physiology. Cell physiology
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article