Inhibitory Effects of Jakyakgamcho-Tang (Glycyrrhiza uralensis and Paeonia lactiflora) on the Pacemaker Potential of the Interstitial Cells of Cajal in the Murine Small Intestine

Abstract

Jakyakgamcho-tang (JYGCT) has been used to treat various diseases. The interstitial cells of Cajal (ICC) regulate gastrointestinal (GI) motility as pacemaker cells. Here, we examined the effects of JYGCT on the pacemaker potential of the ICC in the small intestine. We observed that JYGCT inhibited the pacemaker potential in a dose-dependent manner. Glibenclamide did not affect the pacemaker potential and on these conditions, JYGCT also had no effect on the pacemaker potential. Pretreatment with capsazepine or SB452533 blocked the JYGCT-induced effects. In the presence of SQ-22536, JYGCT did not inhibit the pacemaker potential. Additionally, JYGCT inhibited spontaneous [Ca2+]i oscillations and JYGCT-induced ITR increase was associated with TMEM16A, motilin and substance P activation. Moreover, JYGCT was effective in alleviating the symptoms of irritable bowel syndrome. Our results suggest that JYGCT inhibited the pacemaker potential of the ICC via KATP, the TRPV1 or the cyclic AMP pathway, and intracellular Ca2+ regulation, indicating that JYGCT can affect ICC and thus have the function of regulating GI motility. Therefore, JYGCT may be used as a GI motility disorder regulator or disease prevention agent.