scholarly journals Magnolia Officinalis Bark Extract Induces Depolarization of Pacemaker Potentials Through M2 and M3 Muscarinic Receptors in Cultured Murine Small Intestine Interstitial Cells of Cajal

2017 ◽  
Vol 43 (5) ◽  
pp. 1790-1802 ◽  
Author(s):  
Hyun Jung Kim ◽  
Taewon Han ◽  
Yun Tai Kim ◽  
Insuk So ◽  
Byung Joo Kim
Keyword(s):  
Receptor Antagonist ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Pacemaker Potential ◽  
Pacemaker Potentials ◽  
Magnolia Officinalis ◽  
Cells Of Cajal ◽  
Gi Motility

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.

Distinct roles of nitric oxide synthases and interstitial cells of Cajal in rectoanal relaxation

2005 ◽  
Vol 289 (2) ◽  
pp. G291-G299 ◽  
Author(s):  
Akiko Terauchi ◽  
Daisuke Kobayashi ◽  
Hiroshi Mashimo
Keyword(s):  
Nitric Oxide ◽  
Interstitial Cells Of Cajal ◽  
Electrical Field Stimulation ◽  
Interstitial Cells ◽  
Organ Bath ◽  
Wild Type ◽  
Basal Tone ◽  
Cells Of Cajal

Nitric oxide (NO) relaxes the internal anal sphincter (IAS), but its enzymatic source(s) remains unknown; neuronal (nNOS) and endothelial (eNOS) NO synthase (NOS) isoforms could be involved. Also, interstitial cells of Cajal (ICC) may be involved in IAS relaxation. We studied the relative roles of nNOS, eNOS, and c-Kit-expressing ICC for IAS relaxation using genetic murine models. The basal IAS tone and the rectoanal inhibitory reflex (RAIR) were assessed in vivo by a purpose-built solid-state manometric probe and by using wild-type, nNOS-deficient (nNOS−/−), eNOS-deficient (eNOS−/−), and W/Wv mice (lacking certain c-Kit-expressing ICC) with or without l-arginine or Nω-nitro-l-arginine methyl ester (l-NAME) treatment. Moreover, the basal tone and response to electrical field stimulation (EFS) were studied in organ bath using wild-type and mutant IAS. In vivo, the basal tone of eNOS−/− was higher and W/Wv was lower than wild-type and nNOS−/− mice. l-Arginine administered rectally, but not intravenously, decreased the basal tone in wild-type, nNOS−/−, and W/Wv mice. However, neither l-arginine nor l-NAME affected basal tone in eNOS−/− mice. In vitro, l-arginine decreased basal tone in wild-type and nNOS−/− IAS but not in eNOS−/− or wild-type IAS without mucosa. The in vivo RAIR was intact in wild-type, eNOS−/−, and W/Wv mice but absent in all nNOS−/− mice. EFS-induced IAS relaxation was also reduced in nNOS−/− IAS. Thus the basal IAS tone is largely controlled by eNOS in the mucosa, whereas the RAIR is controlled by nNOS. c-Kit-expressing ICC may not be essential for the RAIR.

scholarly journals Involvement of MAPKs and PLC Pathways in Modulation of Pacemaking Activity by So-Cheong-Ryong-Tang in Interstitial Cells of Cajal from Murine Small Intestine

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Min Woo Hwang ◽  
Hee Jung Lee ◽  
Ho Joon Song ◽  
Byung Joo Kim
Keyword(s):  
Small Intestine ◽  
Receptor Antagonist ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Pacemaker Activity ◽  
Pipette Solution ◽  
Current Clamp Mode ◽  
Pacemaker Potentials ◽  
Cells Of Cajal ◽  
Mapk Inhibitor

Purpose. Interstitial cells of Cajal (ICCs) are the pacemaker cells that generate slow waves in the gastrointestinal (GI) tract. We have aimed to investigate the effects of Socheongryong-Tang (SCRT) in ICCs from mouse’s small intestine.Methods. The whole-cell patch-clamp configuration was used to record membrane potentials from cultured ICCs. Intracellular Ca2+([Ca2+]i) increase was studied in cultured ICCs using fura-2 AM.Results. ICCs generated pacemaker potentials in mouse’s small intestine. SCRT produced membrane depolarization in current clamp mode. Y25130 (5-HT3receptor antagonist) and RS39604 (5-HT4receptor antagonist) blocked SCRT-induced membrane depolarizations, whereas SB269970 (5-HT7receptor antagonist) did not. When GDP-β-S (1 mM) was in the pipette solution, SCRT did not induce the membrane depolarizations.[Ca2+]ianalysis showed that SCRT increased[Ca2+]i. In the presence of PD98059 (p42/44 MAPK inhibitor), SCRT did not produce membrane depolarizations. In addition, SB203580 (p38 MAPK inhibitor) and JNK inhibitors blocked the depolarizations by SCRT in pacemaker potentials. Furthermore, the membrane depolarizations by SCRT were not inhibited by U-73122, an active phospholipase C (PLC) inhibitor, but by U-73343, an inactive PLC inhibitor.Conclusion. These results suggest that SCRT might affect GI motility by the modulation of pacemaker activity through MAPKs and PLC pathways in the ICCs.

scholarly journals The Mechanism of Action of Zingerone in the Pacemaker Potentials of Interstitial Cells of Cajal Isolated from Murine Small Intestine

2018 ◽  
Vol 46 (5) ◽  
pp. 2127-2137 ◽  
Author(s):  
Jung Nam Kim ◽  
Hyun Jung Kim ◽  
Iksung Kim ◽  
Yun Tai Kim ◽  
Byung Joo Kim
Keyword(s):  
Protein Kinase ◽  
Interstitial Cells Of Cajal ◽  
Channel Blocker ◽  
Interstitial Cells ◽  
Transient Receptor Potential Vanilloid ◽  
Gi Tract ◽  
Pacemaker Potential ◽  
Pacemaker Potentials ◽  
Cells Of Cajal ◽  
Mapk Inhibitor

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.

Lack of pyloric interstitial cells of Cajal explains distinct peristaltic motor patterns in stomach and small intestine

2005 ◽  
Vol 289 (3) ◽  
pp. G539-G549 ◽  
Author(s):  
Xuan-Yu Wang ◽  
Wim J. E. P. Lammers ◽  
Premysl Bercik ◽  
Jan D. Huizinga
Keyword(s):  
Slow Wave ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Motor Patterns ◽  
Network Characteristics ◽  
Pyloric Region ◽  
Motor Activities ◽  
Cells Of Cajal

The frequency and propagation velocity of distension-induced peristaltic contractions in the antrum and duodenum are distinctly different and depend on activation of intrinsic excitatory motoneurons as well as pacemaker cells, the interstitial cells of Cajal associated with Auerbach's plexus (ICC-AP). Because ICC are critical for coordination of motor activities along the long axis of many regions in the gut, the role of ICC in antroduodenal coordination was investigated. We used immunohistochemistry, electron microscopy, simultaneous multiple electrical recordings in vitro, and videofluoroscopy in vivo in mice and rats. A strongly reduced number of ICC-AP with loss of network characteristics was observed in a 4-mm area in the rat and a 1-mm area in the mouse pyloric region. The pyloric region showed a slow wave-free gap of 4.1 mm in rats and 1.3 mm in mice. Between antrum and duodenum, there was no interaction of electrical activities and in the absence of gastric emptying, there was no coordination of motor activities. When the pyloric sphincter opened, 2.4 s before the front of the antral wave reached the pylorus, the duodenum distended after receiving gastric content and aboral duodenal peristalsis was initiated, often disrupting other motor patterns. The absence of ICC-AP and slow wave activity in the pyloric region allows the antrum and duodenum to have distinct uncoordinated motor activities. Coordination of aborally propagating peristaltic antral and duodenal activity is initiated by opening of the pylorus, which is followed by distention-induced duodenal peristalsis. Throughout this coordinated motor activity, the pacemaker systems in antrum and duodenum remain independent.

scholarly journals Quercetin Inhibits Pacemaker Potentials via Nitric Oxide/cGMP-Dependent Activation and TRPM7/ANO1 Channels in Cultured Interstitial Cells of Cajal from Mouse Small Intestine

2015 ◽  
Vol 35 (6) ◽  
pp. 2422-2436 ◽  
Author(s):  
Huijin Gim ◽  
Joo Hyun Nam ◽  
Soojin Lee ◽  
Ji Hwan Shim ◽  
Hyun Jung Kim ◽  
...  
Keyword(s):  
Small Intestine ◽  
Opioid Receptor ◽  
Interstitial Cells Of Cajal ◽  
Pacemaker Activity ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Pacemaker Potentials ◽  
Cells Of Cajal ◽  
Gi Motility

Background: Quercetin regulates gastrointestinal (GI) motor activity but the molecular mechanism involved has not been determined. The authors investigated the effects of quercetin, a flavonoid present in various foods, on the pacemaker activities of interstitial cells of Cajal (ICCs) in murine small intestine in vitro and on GI motility in vivo. Materials and Methods: Enzymatic digestion was used to dissociate ICCs from mouse small intestines. The whole-cell patch-clamp configuration was used to record pacemaker potentials in cultured ICCs in the absence or presence of quercetin and to record membrane currents of transient receptor potential melastatin (TRPM) 7 or transmembrane protein 16A (Tmem16A, anoctamin1 (ANO1)) overexpressed in human embryonic kidney (HEK) 293 cells. The in vivo effects of quercetin on GI motility were investigated by measuring the intestinal transit rates (ITRs) of Evans blue in normal mice. Results: Quercetin (100-200 μM) decreased the amplitudes and frequencies of pacemaker activity in a concentration-dependent manner in current clamp mode, but this action was blocked by naloxone (a pan-opioid receptor antagonist) and by GDPβS (a GTP-binding protein inhibitor). However, potassium channels were not involved in these inhibitory effects of quercetin. To study the quercetin signaling pathway, we examined the effects of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of guanylate cyclase, and of RP-8-CPT-cGMPS, an inhibitor of protein kinase G (PKG). These inhibitors blocked the inhibitory effects of quercetin on pacemaker activities. Also, L-NAME (100 μM), a non-selective NO synthase (NOS) inhibitor, blocked the effects of quercetin on pacemaker activity and quercetin stimulated cGMP production. Furthermore, quercetin inhibited both Ca2+-activated Cl- channels (TMEM16A, ANO1) and TRPM7 channels. In vivo, quercetin (10-100 mg/kg, p.o.) decreased ITRs in normal mice in a dose-dependent manner. Conclusions: Quercetin inhibited ICC pacemaker activities by inhibiting TRPM7 and ANO1 via opioid receptor signaling pathways in cultured murine ICCs. The study shows quercetin attenuates GI tract motility, and suggests quercetin be considered the basis for the development of novel spasmolytic agents for the prevention or alleviation of GI motility dysfunctions.

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 ◽  
...  
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Pacemaker Potential ◽  
Cells Of Cajal ◽  
Potential Frequency

scholarly journals Menthol Modulates Pacemaker Potentials through TRPA1 Channels in Cultured Interstitial Cells of Cajal from Murine Small Intestine

2016 ◽  
Vol 38 (5) ◽  
pp. 1869-1882 ◽  
Author(s):  
Hyun Jung Kim ◽  
Jinhong Wie ◽  
Insuk So ◽  
Myeong Ho Jung ◽  
Ki-Tae Ha ◽  
...  
Keyword(s):  
Small Intestine ◽  
Membrane Potential ◽  
Interstitial Cells Of Cajal ◽  
Rho Kinase ◽  
Thromboxane A2 ◽  
Interstitial Cells ◽  
Dependent Manner ◽  
Induced Membrane ◽  
Pacemaker Potentials ◽  
Cells Of Cajal

Background/Aims: ICCs are the pacemaker cells responsible for slow waves in gastrointestinal (GI) smooth muscle, and generate periodic pacemaker potentials in current-clamp mode. Methods: The effects of menthol on the pacemaker potentials of cultured interstitial cells of Cajal (ICCs) from mouse small intestine were studied using the whole cell patch clamp technique. Results: Menthol (1 - 10 μM) was found to induce membrane potential depolarization in a concentration-dependent manner. The effects of various TRP channel antagonists were examined to investigate the receptors involved. The addition of the TRPM8 antagonist, AMTB, did not block menthol-induced membrane potential depolarizations, but TRPA1 antagonists (A967079 or HC-030031) blocked the effects of menthol, as did intracellular GDPβS. Furthermore, external and internal Ca2+ levels were found to depolarize menthol-induced membrane potentials, whereas external Na+ was not. Y-27632 (a Rho kinase inhibitor), SC-560 (a selective COX 1 inhibitor), NS-398 (a selective COX 2 inhibitor), ozagrel (a thromboxane A2 synthase inhibitor) and SQ-29548 (highly selective thromboxane receptor antagonist) were used to investigate the involvements of Rho-kinase, cyclooxygenase (COX), and the thromboxane pathway in menthol-induced membrane potential depolarizations, and all inhibitors were found to block the effect of menthol. Conclusions: These results suggest that menthol-induced membrane potential depolarizations occur in a G-protein-, Ca2+-, Rho-kinase-, COX-, and thromboxane A2-dependent manner via TRPA1 receptor in cultured ICCs in murine small intestine. The study shows ICCs are targeted by menthol and that this interaction can affect intestinal motility.

Rikkunshito Depolarizes Pacemaker Potentials of Cultured Interstitial Cells of Cajal through Ghrelin Receptors in Murine Small Intestine

Digestion ◽  
2019 ◽  
Vol 101 (3) ◽  
pp. 227-238 ◽  
Author(s):  
Jeong Nam Kim ◽  
Joo Hyun Nam ◽  
Jong Rok Lee ◽  
Sang Chan Kim ◽  
Young Kyu Kwon ◽  
...  
Keyword(s):  
Small Intestine ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Pacemaker Potentials ◽  
Ghrelin Receptors ◽  
Murine Small Intestine ◽  
Cells Of Cajal
Sign in / Sign up

Export Citation Format

Share Document