Basal cGMP regulates the resting pacemaker potential frequency of cultured mouse colonic interstitial cells of Cajal

2014 ◽  
Vol 387 (7) ◽  
pp. 641-648 ◽  
Author(s):  
Pawan Kumar Shahi ◽  
Seok Choi ◽  
Yu Jin Jeong ◽  
Chan Guk Park ◽  
Insuk So ◽  
...  
2017 ◽  
Vol 43 (5) ◽  
pp. 1790-1802 ◽  
Author(s):  
Hyun Jung Kim ◽  
Taewon Han ◽  
Yun Tai Kim ◽  
Insuk So ◽  
Byung Joo Kim

Background: Magnolia officinalis Rehder and EH Wilson (M. officinalis) are traditional Chinese medicines widely used for gastrointestinal (GI) tract motility disorder in Asian countries. We investigated the effects of an ethanol extract of M. officinalis (MOE) on the pacemaker potentials of cultured interstitial cells of Cajal (ICCs) in vitro and its effects on GI motor functions in vivo. Methods: We isolated ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record the pacemaker potentials in cultured ICCs in vitro. Both gastric emptying (GE) and intestinal transit rates (ITRs) were investigated in normal and GI motility dysfunction (GMD) mice models in vivo. Results: MOE depolarized ICC pacemaker potentials dose-dependently. Pretreatment with methoctramine (a muscarinic M2 receptor antagonist) and 4-DAMP (a muscarinic M3 receptor antagonist) inhibited the effects of MOE on the pacemaker potential relative to treatment with MOE alone. In addition, MOE depolarized pacemaker potentials after pretreatment with Y25130 (a 5-HT3 receptor antagonist), GR113808 (a 5-HT4 receptor antagonist) or SB269970 (a 5-HT7 receptor antagonist). However, pretreatment with RS39604 (a 5-HT4 receptor antagonist) blocked MOE-induced pacemaker potential depolarizations. Intracellular GDPβS inhibited MOE-induced pacemaker potential depolarization, as did pretreatment with Ca2+ free solution or thapsigargin. In normal mice, the GE and ITR values were significantly and dose-dependently increased by MOE. In loperamide-and cisplatin-induced GE delay models, MOE administration reversed the GE deficits. The ITRs of the GMD mice were significantly reduced relative to those of normal mice, which were significantly and dose-dependently reversed by MOE. Conclusion: These results suggest that MOE dose-dependently depolarizes ICCs pacemaker potentials through M2 and M3 receptors via internal and external Ca2+ regulation through G protein pathways in vitro. Moreover, MOE increased GE and ITRs in vivo in normal and GMD mouse models. Taken together, the results of this study show that MOE have the potential for development as a gastroprokinetic agent in GI motility function.


2014 ◽  
Vol 116 (1) ◽  
pp. 56-69 ◽  
Author(s):  
Jae Boum Youm ◽  
Chae Hun Leem ◽  
Sung Ryul Lee ◽  
In-Sung Song ◽  
Hyoung Kyu Kim ◽  
...  

2018 ◽  
Vol 46 (5) ◽  
pp. 2127-2137 ◽  
Author(s):  
Jung Nam Kim ◽  
Hyun Jung Kim ◽  
Iksung Kim ◽  
Yun Tai Kim ◽  
Byung Joo Kim

Background/Aims: Zingerone, a major component found in ginger root, is clinically effective for the treatment of various diseases. Interstitial cells of Cajal (ICCs) are the pacemaker cells responsible for slow waves in the gastrointestinal (GI) tract. We investigated the effects of zingerone on the pacemaker potentials of ICCs to assess its mechanisms of action and its potential as a treatment for GI tract motility disorder. Methods: We isolated ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record the pacemaker potentials in cultured ICCs. Results: Under the current clamping mode, zingerone inhibited pacemaker potentials of ICCs concentration-dependently. These effects were blocked not by capsazepine, a transient receptor potential vanilloid 1 (TRPV1) channel blocker, but by glibenclamide, a specific ATP-sensitive K+ channel blocker. Pretreatment with SQ-22536 (an adenylate cyclase inhibitor), LY294002 (a phosphoinositide 3-kinase inhibitor), and calphostin C (a protein kinase C (PKC) inhibitor) did not block the effects of zingerone on the pacemaker potentials relative to treatment with zingerone alone. However, zingerone-induced pacemaker potential inhibition was blocked by 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ; a guanylate cyclase inhibitor), KT5823 (a protein kinase G (PKG) inhibitor), and L-NAME (a non-selective nitric oxide synthase (NOS) inhibitor). In addition, zingerone stimulated cyclic guanosine monophosphate (cGMP) production in ICCs. Finally, pretreatment with PD98059 (a p42/44 mitogen-activated protein kinase (MAPK) inhibitor), SB203580 (a p38 MAPK inhibitor), and SP600125 (c–Jun N–terminal kinases (JNK)–specific inhibitor) blocked the zingerone-induced pacemaker potential inhibition. Conclusion: These results suggest that zingerone concentration-dependently inhibits pacemaker potentials of ICCs via NO/cGMP-dependent ATP-sensitive K+ channels through MAPK-dependent pathways. Taken together, this study shows that zingerone may have the potential for development as a GI regulation agent.


2001 ◽  
Vol 120 (5) ◽  
pp. A201-A201 ◽  
Author(s):  
P STREGE ◽  
A RICH ◽  
Y OU ◽  
S GIBBONS ◽  
M SARR ◽  
...  

2020 ◽  
Vol 20 (3) ◽  
pp. 240-246
Author(s):  
Heng Yang ◽  
Xiao-Ju Jin ◽  
Hong Luo ◽  
Yuan-Hai Li

Objective: This study aims to investigate the effect of morphine with naloxone on intestinal peristalsis and the number of interstitial cells of Cajal (ICC) in colon tissues of rabbits. Methods: Thirty rabbits were randomly divided into five groups (n=6, each group): saline control group (NS group), low concentration of morphine group (L group), medium concentration of morphine group (M group), high concentration of morphine group (H group), medium concentration of morphine and naloxone mixed with antagonist group (NM group). Rabbits in these five groups were administered with an epidural puncture tube and dorsal epidural analgesia pump, and were continuously infused for seven days. Fecal characteristics were observed, and the ink propulsion rate was calculated. The expression level of ICC C-kit protein in colon tissues was tested by western blot. Results: The stool characteristics in the L, M and H groups were more severe than those in the NS and NM groups. Furthermore, the intestinal propulsion rate in the L, M and H groups was lower than that in the NS and NM groups. The C-kit mRNA and protein expression in the colon of rabbits were significantly lower in the L, M and H groups, when compared to the NS and NM groups. Conclusions: Naloxone blocked the mRNA and protein expression of C-kit, and improved intestinal motor function.


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