Propofol inhibits expression of angiotensin II receptor type 2 in dorsal root ganglion neurons

Abstract

The renin-angiotensin system (RAS) is involved in nociception and has functions in the cardiovascular system. The primary role of the RAS is to mediate the effect of angiotensin II (Ang II) through Ang II receptor type 2 (AT2). Due to this, AT2 has become a novel therapeutic target for the relief of peripheral neuropathic pain in humans. As it is one of the most popular induction agents of general anesthesia, propofol also exerts peripheral antinociceptive effects. The present study assessed the effect of propofol on the expression of AT2 in cultured dorsal root ganglion (DRG) neurons. The results indicate that propofol decreases AT2 mRNA expression in a statistically significant dose- and time-dependent manner (P<0.05). This resulted in a marked decrease in AT2 protein expression and the density of Ang II-binding AT2 on the cell membrane of DRG neurons. The effect of propofol was reversed by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. Although propofol exhibited no significant effect on AT2 gene promoter activity, it significantly decreased the stability of AT2 mRNA (P<0.05). However, this effect was reversed by LY294002. In addition, propofol increased PI3K activity in a concentration-dependent manner in DRG neurons. In conclusion, to the best of our knowledge, the current study provides the first evidence suggesting that propofol inhibits the expression of AT2 in DRG neurons by decreasing the stability of AT2 mRNA through a PI3K-dependent mechanism. The present study provides novel insights into the mechanisms of the peripheral antinociceptive action of propofol and suggests a potential means of regulating Ang II/AT2 signaling in the peripheral nervous system.