Magnolia Officinalis Bark Extract Induces Depolarization of Pacemaker Potentials Through M 2 and M 3 Muscarinic Receptors in Cultured Murine Small Intestine Interstitial Cells of Cajal

Hyun Jung Kim, Taewon Han, Yun Tai Kim, Insuk So, Byung Joo Kim

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

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 M 2 receptor antagonist) and 4-DAMP (a muscarinic M 3 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-HT 3 receptor antagonist), GR113808 (a 5-HT 4 receptor antagonist) or SB269970 (a 5-HT 7 receptor antagonist). However, pretreatment with RS39604 (a 5-HT 4 receptor antagonist) blocked MOE-induced pacemaker potential depolarizations. Intracellular GDPβS inhibited MOE-induced pacemaker potential depolarization, as did pretreatment with Ca 2+ 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 M 2 and M 3 receptors via internal and external Ca 2+ 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.

Original languageEnglish
Pages (from-to)1790-1802
Number of pages13
JournalCellular Physiology and Biochemistry
Volume43
Issue number5
DOIs
StatePublished - 1 Jan 2018

Fingerprint

Magnolia
Interstitial Cells of Cajal
Gastric Emptying
Muscarinic Receptors
Serotonin Receptors
Small Intestine
Gastrointestinal Motility
Cholinergic Agents
Cultured Cells
Loperamide
Thapsigargin
Chinese Traditional Medicine
GTP-Binding Proteins
Cisplatin
Gastrointestinal Tract
Ethanol
In Vitro Techniques

Keywords

  • Gastric Emptying
  • Gastrointestinal Motility
  • Interstitial Cells of Cajal
  • Intestinal Transit Rates
  • M. officinalis
  • Magnolia officinalis Rehder and EH Wilson
  • Pacemaker Potentials

Cite this

@article{dd1e9d6b45e94609983abf11834d3c0d,
title = "Magnolia Officinalis Bark Extract Induces Depolarization of Pacemaker Potentials Through M 2 and M 3 Muscarinic Receptors in Cultured Murine Small Intestine Interstitial Cells of Cajal",
abstract = "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 M 2 receptor antagonist) and 4-DAMP (a muscarinic M 3 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-HT 3 receptor antagonist), GR113808 (a 5-HT 4 receptor antagonist) or SB269970 (a 5-HT 7 receptor antagonist). However, pretreatment with RS39604 (a 5-HT 4 receptor antagonist) blocked MOE-induced pacemaker potential depolarizations. Intracellular GDPβS inhibited MOE-induced pacemaker potential depolarization, as did pretreatment with Ca 2+ 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 M 2 and M 3 receptors via internal and external Ca 2+ 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.",
keywords = "Gastric Emptying, Gastrointestinal Motility, Interstitial Cells of Cajal, Intestinal Transit Rates, M. officinalis, Magnolia officinalis Rehder and EH Wilson, Pacemaker Potentials",
author = "Kim, {Hyun Jung} and Taewon Han and Kim, {Yun Tai} and Insuk So and Kim, {Byung Joo}",
year = "2018",
month = "1",
day = "1",
doi = "10.1159/000484065",
language = "English",
volume = "43",
pages = "1790--1802",
journal = "Cellular Physiology and Biochemistry",
issn = "1015-8987",
publisher = "S. Karger AG",
number = "5",

}

Magnolia Officinalis Bark Extract Induces Depolarization of Pacemaker Potentials Through M 2 and M 3 Muscarinic Receptors in Cultured Murine Small Intestine Interstitial Cells of Cajal . / Kim, Hyun Jung; Han, Taewon; Kim, Yun Tai; So, Insuk; Kim, Byung Joo.

In: Cellular Physiology and Biochemistry, Vol. 43, No. 5, 01.01.2018, p. 1790-1802.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Magnolia Officinalis Bark Extract Induces Depolarization of Pacemaker Potentials Through M 2 and M 3 Muscarinic Receptors in Cultured Murine Small Intestine Interstitial Cells of Cajal

AU - Kim, Hyun Jung

AU - Han, Taewon

AU - Kim, Yun Tai

AU - So, Insuk

AU - Kim, Byung Joo

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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 M 2 receptor antagonist) and 4-DAMP (a muscarinic M 3 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-HT 3 receptor antagonist), GR113808 (a 5-HT 4 receptor antagonist) or SB269970 (a 5-HT 7 receptor antagonist). However, pretreatment with RS39604 (a 5-HT 4 receptor antagonist) blocked MOE-induced pacemaker potential depolarizations. Intracellular GDPβS inhibited MOE-induced pacemaker potential depolarization, as did pretreatment with Ca 2+ 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 M 2 and M 3 receptors via internal and external Ca 2+ 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.

AB - 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 M 2 receptor antagonist) and 4-DAMP (a muscarinic M 3 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-HT 3 receptor antagonist), GR113808 (a 5-HT 4 receptor antagonist) or SB269970 (a 5-HT 7 receptor antagonist). However, pretreatment with RS39604 (a 5-HT 4 receptor antagonist) blocked MOE-induced pacemaker potential depolarizations. Intracellular GDPβS inhibited MOE-induced pacemaker potential depolarization, as did pretreatment with Ca 2+ 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 M 2 and M 3 receptors via internal and external Ca 2+ 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.

KW - Gastric Emptying

KW - Gastrointestinal Motility

KW - Interstitial Cells of Cajal

KW - Intestinal Transit Rates

KW - M. officinalis

KW - Magnolia officinalis Rehder and EH Wilson

KW - Pacemaker Potentials

UR - http://www.scopus.com/inward/record.url?scp=85031827674&partnerID=8YFLogxK

U2 - 10.1159/000484065

DO - 10.1159/000484065

M3 - Article

VL - 43

SP - 1790

EP - 1802

JO - Cellular Physiology and Biochemistry

JF - Cellular Physiology and Biochemistry

SN - 1015-8987

IS - 5

ER -