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

Various heterotrimeric G protein betagamma subunits (Gbetagamma) are region-specifically expressed in brain where associated with "stress-axis", however, the role of Gbetagamma-mediated signaling in regulating stress is unknown. This study was designed to examine the changes of Gbetagamma expression and Gbetagamma-mediated signaling in rat brain by stress. Experimental stress was induced by immobilization (2h/day for 7 days) and the level of mRNAs and proteins for Gbeta(1-5), 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 Gbeta(1-5) in brain regions associated with stress was increased in stressed animals. Especially, a significant increase in Gbetas 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 Gbetagamma-mediated PKB/Akt and ERK1/2 signaling pathway by increasing the expression of Gbetas to regulate the physiological responses.