Back to Search
Start Over
Zuojin Pill enhances gastrointestinal motility by modulating the pacemaker potentials in interstitial cells of Cajal through multiple signaling pathways.
Zuojin Pill enhances gastrointestinal motility by modulating the pacemaker potentials in interstitial cells of Cajal through multiple signaling pathways.
- Source :
-
International journal of medical sciences [Int J Med Sci] 2024 Oct 28; Vol. 21 (15), pp. 2883-2896. Date of Electronic Publication: 2024 Oct 28 (Print Publication: 2024). - Publication Year :
- 2024
-
Abstract
- Zuojin Pill (ZJP) is a traditional herbal preparation used to treat various gastrointestinal (GI) disorders. The purpose of this study was to elucidate the underlying cellular and molecular mechanisms by evaluating the effects of ZJP on the pacemaker activity of isolated interstitial cells of Cajal (ICCs) and on in vivo GI motility in mice. We isolated ICCs from mouse small intestine and measured pacemaker potentials by whole-cell patch clamping as well as intracellular calcium signaling by microfluorometry. Intestinal transit rate (ITR) was measured by Evans Blue migration. Administration of ZJP depolarized ICCs and reduced the amplitude and frequency of pacemaker potentials. Pretreatment with the 5-HT4 receptor antagonist RS39604, administration of the muscarinic M3 receptor antagonist 4-DAMP, or intracellular perfusion of the G-protein inhibitor GDP-β-S blocked ZJP-induced ICCs depolarization. In addition, external calcium-free medium and administration of the Ca <superscript>2+</superscript> -ATPase inhibitor thapsigargin, which depletes intracellular calcium stores, also blocked ZJP-induced ICCs depolarization. Moreover, ZJP-induced ICCs depolarization was inhibited in the presence of the phospholipase C (PLC) inhibitor U-73122, IP <subscript>3</subscript> -dependent Ca <superscript>2+</superscript> release inhibitor xestospongin C, or various mitogen-activated protein kinase (MAPK) inhibitors. Alternatively, ZJP-induced ICCs depolarization in the presence of protein kinase C (PKC) inhibitors. Furthermore, ZJP reversed the reduction of ITR caused by loperamide (Imodium) and normalized the ITR abnormality of two etiologically distinct GI motility disorder (GMD) mouse models. Finally, ZJP increased serum concentrations of the pro-peristalsis factors motilin and substance P. Our results suggest that ZJP depolarizes ICCs via 5-HT4 or muscarinic M3 receptor activation and G-protein dependent calcium-, PLC-, inositol triphosphate-, and MAPK signaling pathways (but not PKC-dependent pathways), leading to enhanced GI motility.<br />Competing Interests: Competing Interests: The authors have declared that no competing interest exists.<br /> (© The author(s).)
- Subjects :
- Animals
Mice
Signal Transduction drug effects
Calcium Signaling drug effects
Intestine, Small drug effects
Intestine, Small metabolism
Receptor, Muscarinic M3 metabolism
Receptor, Muscarinic M3 antagonists & inhibitors
Receptor, Muscarinic M3 genetics
Male
Patch-Clamp Techniques
Humans
Piperidines
Interstitial Cells of Cajal drug effects
Interstitial Cells of Cajal metabolism
Gastrointestinal Motility drug effects
Drugs, Chinese Herbal pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1449-1907
- Volume :
- 21
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- International journal of medical sciences
- Publication Type :
- Academic Journal
- Accession number :
- 39628697
- Full Text :
- https://doi.org/10.7150/ijms.103507