Stress induces the expression of heterotrimeric G protein β subunits and the phosphorylation of PKB/Akt and ERK1/2 in rat brain

Various heterotrimeric G protein βγ subunits (Gβγ) are region-specifically expressed in brain where associated with “stress-axis”, however, the role of Gβγ-mediated signaling in regulating stress is unknown. This study was designed to examine the changes of Gβγ expression and Gβγ-mediated signaling in rat brain by stress. Experimental stress was induced by immobilization (2 h/day for 7 days) and the level of mRNAs and proteins for Gβ1–5, and the phosphorylation of PKB/Akt (phosphatidylinositol 3-kinase-linked protein kinase B) and ERK1/2 (extracellular signal-regulated kinase 1/2) were measured in five different regions of rat brain including frontal cortex, striatum, hypothalamus, hippocampus, and cerebellum. As compared in not-handled non-stressed animals, the expression of both mRNAs and proteins for Gβ1–5 in brain regions associated with stress was increased in stressed animals. Especially, a significant increase in Gβs immunoreactivity in the caudate putamen, the paraventricular nucleus of the hypothalamus (PVN), and the dentate gyrus of the hippocampus (DG) of stressed rats was observed. Stress significantly induced the phosphorylation of PKB/Akt and ERK1/2 in striatum, hypothalamus and hippocampus. Therefore, these results suggest that stress may activate, at least in part, the Gβγ-mediated PKB/Akt and ERK1/2 signaling pathway by increasing the expression of Gβs to regulate the physiological responses.