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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kim, Byung Joo Kim, Hyungwoo Lee, Guem San So, Insuk Kim, Seon Jeong |
| Description | Author Affiliation: Kim BJ ( Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 626-870, Republic of Korea. Electronic address: vision@pusan.ac.kr.); Kim H ( Division of Pharmacology, Pusan National University School of Korean Medicine, Yangsan 626-870, Republic of Korea.); Lee GS ( Wonkwang University College of Korean Medicine, Iksan 570-749, Republic of Korea.); So I ( Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.); Kim SJ ( Center for Bio-Artificial Muscle and Department of Biomedical Engineering, Hanyang University, Seoul 133-791, Republic of Korea. Electronic address: sjk@hanyang.ac.kr.) |
| Abstract | ETHNOPHARMACOLOGICAL RELEVANCE: San-Huang-Xie-Xin-Tang (SHXXT) is a traditional Chinese medicinal formula composed of Coptidis rhizoma (Coptis chinesis Franch), Scutellariae radix (Scutellaria baicalensis Georgi), and Rhei rhizoma (Rheum officinale Baill) and is widely used in Eastern Asia, especially to ameliorate the symptoms of gastrointestinal (GI) disorders related to gastritis, gastric bleeding, peptic ulcers, and abnormal GI motility AIM OF THE STUDY: Interstitial cells of Cajal (ICCs) are pacemaker cells in the GI tract that generate rhythmic oscillations in membrane potentials known as slow waves. Because GI disorders, especially abnormal GI motility, are major lifelong problems, the authors investigated the effects of SHXXT on mouse small intestine ICCs, and sought to identify the receptors and the action mechanisms involved. MATERIALS AND METHODS: Enzymatic digestions were used to dissociate ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record potentials generated by cultured ICCs. RESULTS: SHXXT produced membrane depolarization in current-clamp mode, and Y25130 (a 5-HT3 receptor antagonist) and RS39604 (a 5-HT4 receptor antagonist) blocked SHXXT-induced membrane depolarizations, whereas SB269970 (a 5-HT7 receptor antagonist) did not. However, during external Ca2+ free conditions or in the presence of thapsigargin, SHXXT did not exhibit membrane depolarization. Furthermore, the application of flufenamic acid (a nonselective cation channel (NSCC) blocker) or DIDS (a chloride channel blocker) abolished pacemaker potential generation and blocked SHXXT-induced membrane depolarizations. In addition, SHXXT-induced membrane depolarizations, which are dependent on G-protein, in ICCs were blocked by PD 98059 (a p42/44 mitogen-activated protein kinase (MAPK) inhibitor), SB203580 (a p38 MAPK inhibitor), and by a c-jun NH2-terminal kinase (JNK) II inhibitor. Regarding the components of SHXXT, Coptidis rhizome and Rhei rhizoma modulated ICC pacemaking activity, whereas Scutellariae radix did not. CONCLUSION: SHXXT modulates pacemaker potentials via 5-HT3 and 5-HT4 receptor-mediated pathways, external Ca2+ influx, and Ca2+ release from internal stores. Furthermore, NSCCs and Cl- channels play important roles in the regulation of pacemaking activity in a MAPK dependent manner in ICCs. The regulation of pacemaking activity by SHXXT may be due to the activity of Coptidis rhizome and Rhei rhizome. The study shows SHXXT can modulate the pacemaking activity of ICCs in the GI tract, and thus, suggests SHXXT has potential pharmacological relevance for the treatment of GI motility disorders. |
| File Format | HTM / HTML |
| ISSN | 03788741 |
| Issue Number | 1 |
| Volume Number | 155 |
| e-ISSN | 18727573 |
| Journal | Journal of Ethnopharmacology |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2014-08-08 |
| Publisher Place | Ireland |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Ethnopharmacology Drugs, Chinese Herbal Pharmacology Interstitial Cells Of Cajal Drug Effects Intestine, Small Membrane Potentials Animals Calcium Metabolism Chloride Channels Female Cytology Male Mice Mice, Inbred Balb C Mitogen-activated Protein Kinases Patch-clamp Techniques Receptors, Serotonin, 5-ht3 Receptors, Serotonin, 5-ht4 Journal Article |
| Content Type | Text |
| Resource Type | Article |
| Subject | Drug Discovery Pharmacology |
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