The causal role of
ammonium in
hepatic encephalopathy was identified in 1930s. Astroglial cells are primary cellular elements of
hepatic encephalopathy which conceptually, can be considered a toxic astrogliopathology. Previously we have reported that acute exposure to
ammonium activated
ouabain/Na,K-
ATPase signalling pathway, which includes Src,
EGF receptor, Raf, Ras,
MEK and ERK1/2. Chronic incubation of astrocytes with
ammonium increased production of endogenous
ouabain-like compound.
Ouabain antagonist
canrenone abolished effects of
ammonium on astrocytic swelling, ROS production, and upregulation of gene expression and function of TRPC1 and Cav1.2. However,
ammonium induces multiple pathological modifications in astrocytes, and some of them may be not related to this signalling pathway. In this review, we focus on the effect of
ammonium on
ouabain/Na,K-
ATPase signalling pathway and its involvement in
ammonium-induced ROS production, cell swelling and aberration of Ca(2+) signals in astrocytes. We also briefly discuss Na,K-
ATPase,
EGF receptor, endogenous
ouabain and
ouabain antagonist.