Salvia miltiorrhiza induces depolarization of pacemaker potentials in murine small intestinal interstitial cells of Cajal via extracellular Ca²⁺ and Na⁺ influx

Abstract

interstitial cells of cajal (iccs) are pacemaker cells that control smooth muscle contraction in the gastrointestinal (Gi) tract. The present study investigated the effects of Salvia miltiorrhiza (SM) on the pacemaker potentials of iccs from the mouse small intestine in vitro and on Gi motility in vivo. The whole-cell patch-clamp configuration was used to record pacemaker potential in iccs in vitro, and Gi motility was investigated in vivo by recording intestinal transit rate (ITR). Using the whole-cell patch-clamp configuration, SM depolarized the pacemaker potentials of iccs in a dose-dependent manner. Fulvestrant blocked SM-induced effects but 1,3-dihydro-3,3-bis(4-hydroxyphenyl)-7methyl-2H-indol-2-one did not. additionally, 4-[2-phenyl-5,7-bis(trifluoromethyl) pyrazolo[1,5-a]pyrimidin-3-yl] phenol blocked SM-induced effects. intracellular guanosine 5'-o-(2-thiodiphosphate), and pretreatment with extracellular ca 2+ -and na + -free solutions also blocked SM-induced effects. Furthermore, iTr values were increased by SM in vivo and SM elevated the levels of motilin (MTl). The SM-induced increase in iTr was associated with increased protein expression levels of c-kit and the transmembrane protein 16a (TMeM16a) channel. in addition, SM induced pacemaker potential depolarization through estrogen receptor β in a G protein-dependent manner via extracellular ca 2+ and na + regulation in the murine small intestine in vitro. Moreover, SM increased the iTr in vivo through the MTl hormone via c-kit and TMeM16a-dependent pathways. Taken together, these results suggested that SM may have the ability to control Gi motility and could be used as a Gi motility regulator.

Effects of black garlic on the pacemaker potentials of interstitial cells of Cajal in murine small intestine in vitro and on gastrointestinal motility in vivo

“…After 1 h of incubation with a blocking buffer, PVDF membranes were probed with anti-5-HT 3 receptor (Abcam, Cambridge, UK), anti-5-HT 4 receptor (Abcam, Cambridge, UK), anti-5-HT 7 receptor (Mybiosource, San Diego, CA, U.S.A.), and anti-β-actin (Santa Cruz Biotechnology, Dallas, TX, U.S.A.) antibodies. Other experiments are the same as in previous studies (Han et al 2021 ).…”

Testosterone secretion is affected by receptor tyrosine kinase c-Kit and anoctamin 1 activation in mouse Leydig cells

“…Ca 2+ signaling activated by LH induces membrane depolarization and depolarized membrane potential induces Ca 2+ influx. Depolarization of pacemaker potential induces hormone secretion (Han et al, 2021). Enhanced Ca 2+ signaling may be involved in the induction of testosterone secretion.…”

Network Pharmacological Analysis and Experimental Validation of the Effect of Smilacis Glabrae Rhixoma on Gastrointestinal Motility Disorder

“…Accordingly, the SGR extract appeared to be safe and did not elicit acute toxicity for a single oral dose of at least 5 g/kg or below. In this paper, SGR 0.01 g/kg, 0.1 g/kg, and 1 g/kg were used in the animal experiment, and this concentration has been widely used in the mouse gastrointestinal animal experiments [ 33 , 37 , 40 , 41 , 42 , 48 , 49 , 50 , 51 ]. When converted to human concentration, 1 g/kg for a mouse is 4.9 g for adults (60 kg) [ 52 ], which is less than the typical human dose of 15–60 g [ 23 ].…”