Inhibitory effect of sanguinarine on PKC-CPI-17 pathway mediating by muscarinic receptors in dispersed intestinal smooth muscle cells

Abstract

This study investigated the inhibitory effects of sanguinarine (SA) on PKC-CPI-17 pathway in rat intestinal smooth muscle cells (ISMC). Previous studies indicate that the inhibitory effects of SA on ISMC contraction are possibly mediated by the Ca(2+) influx. ISMC was treated with 1 μM SA for 24h remarkably inhibited the mRNA expression of m2 and m3 receptors. ISMC treated with 1 or 3 μM SA for 30 min significantly decreased the mRNA expression of PKC-δ, PKC-ε, PKC-η, and CPI-17. 1 μM SA could markedly inhibit carbachol (CCh)-mediated increase PKC-δ, PKC-η, and CPI-17 mRNA but had no effect in PKC-ε.Treatment of ISMC with SA (1 μM, 30 min) caused a decrease in protein expression of PKC-δ. However, the expression of CPI-17 was significantly inhibited in a time-dependent manner. These results demonstrate that the inhibitory effect of SA is coupled with alteration of PKC-mediated signal transduction and intracellular Ca(2+) concentration.

Keywords: Ca(2+); Intestinal smooth muscle cells (ISMC); M receptors; PKC-CPI-17 pathway; Sanguinarine (SA).