Salvia miltiorrhiza Induces Tonic Contraction of the Lower Esophageal Sphincter in Rats via Activation of Extracellular Ca(2+) Influx

Up to 40% of patients with gastroesophageal reflux disease (GERD) suffer from proton pump inhibitor refractory GERD but clinically the medications to strengthen the lower esophageal sphincter (LES) to avoid irritating reflux are few in number. This study aimed to examine whether Salvia miltiorrhiza...

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Autores principales: Tsai, Ching-Chung, Chang, Li-Ching, Huang, Shih-Che, Tey, Shu-Leei, Hsu, Wen-Li, Su, Yu-Tsun, Liu, Ching-Wen, Tsai, Tong-Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331792/
https://www.ncbi.nlm.nih.gov/pubmed/26270658
http://dx.doi.org/10.3390/molecules200814504
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author Tsai, Ching-Chung
Chang, Li-Ching
Huang, Shih-Che
Tey, Shu-Leei
Hsu, Wen-Li
Su, Yu-Tsun
Liu, Ching-Wen
Tsai, Tong-Rong
author_facet Tsai, Ching-Chung
Chang, Li-Ching
Huang, Shih-Che
Tey, Shu-Leei
Hsu, Wen-Li
Su, Yu-Tsun
Liu, Ching-Wen
Tsai, Tong-Rong
author_sort Tsai, Ching-Chung
collection PubMed
description Up to 40% of patients with gastroesophageal reflux disease (GERD) suffer from proton pump inhibitor refractory GERD but clinically the medications to strengthen the lower esophageal sphincter (LES) to avoid irritating reflux are few in number. This study aimed to examine whether Salvia miltiorrhiza (SM) extracts induce tonic contraction of rat LES ex vivo and elucidate the underlying mechanisms. To investigate the mechanism underlying the SM extract-induced contractile effects, rats were pretreated with atropine (a muscarinic receptor antagonist), tetrodotoxin (a sodium channel blocker), nifedipine (a calcium channel blocker), and Ca(2+)-free Krebs-Henseleit solution with ethylene glycol tetraacetic acid (EGTA), followed by administration of cumulative dosages of SM extracts. SM extracts induced dose-related tonic contraction of the LES, which was unaffected by tetrodotoxin, atropine, or nifedipine. However, the SM extract-induced LES contraction was significantly inhibited by Ca(2+)-free Krebs-Henseleit solution with EGTA. Next, SM extracts significantly induce extracellular Ca(2+) entry into primary LES cells in addition to intracellular Ca(2+) release and in a dose-response manner. Confocal fluorescence microscopy showed that the SM extracts consistently induced significant extracellular Ca(2+)influx into primary LES cells in a time-dependent manner. In conclusion, SM extracts could induce tonic contraction of LES mainly through the extracellular Ca(2+) influx pathway.
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spelling pubmed-63317922019-01-24 Salvia miltiorrhiza Induces Tonic Contraction of the Lower Esophageal Sphincter in Rats via Activation of Extracellular Ca(2+) Influx Tsai, Ching-Chung Chang, Li-Ching Huang, Shih-Che Tey, Shu-Leei Hsu, Wen-Li Su, Yu-Tsun Liu, Ching-Wen Tsai, Tong-Rong Molecules Article Up to 40% of patients with gastroesophageal reflux disease (GERD) suffer from proton pump inhibitor refractory GERD but clinically the medications to strengthen the lower esophageal sphincter (LES) to avoid irritating reflux are few in number. This study aimed to examine whether Salvia miltiorrhiza (SM) extracts induce tonic contraction of rat LES ex vivo and elucidate the underlying mechanisms. To investigate the mechanism underlying the SM extract-induced contractile effects, rats were pretreated with atropine (a muscarinic receptor antagonist), tetrodotoxin (a sodium channel blocker), nifedipine (a calcium channel blocker), and Ca(2+)-free Krebs-Henseleit solution with ethylene glycol tetraacetic acid (EGTA), followed by administration of cumulative dosages of SM extracts. SM extracts induced dose-related tonic contraction of the LES, which was unaffected by tetrodotoxin, atropine, or nifedipine. However, the SM extract-induced LES contraction was significantly inhibited by Ca(2+)-free Krebs-Henseleit solution with EGTA. Next, SM extracts significantly induce extracellular Ca(2+) entry into primary LES cells in addition to intracellular Ca(2+) release and in a dose-response manner. Confocal fluorescence microscopy showed that the SM extracts consistently induced significant extracellular Ca(2+)influx into primary LES cells in a time-dependent manner. In conclusion, SM extracts could induce tonic contraction of LES mainly through the extracellular Ca(2+) influx pathway. MDPI 2015-08-11 /pmc/articles/PMC6331792/ /pubmed/26270658 http://dx.doi.org/10.3390/molecules200814504 Text en © 2015 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tsai, Ching-Chung
Chang, Li-Ching
Huang, Shih-Che
Tey, Shu-Leei
Hsu, Wen-Li
Su, Yu-Tsun
Liu, Ching-Wen
Tsai, Tong-Rong
Salvia miltiorrhiza Induces Tonic Contraction of the Lower Esophageal Sphincter in Rats via Activation of Extracellular Ca(2+) Influx
title Salvia miltiorrhiza Induces Tonic Contraction of the Lower Esophageal Sphincter in Rats via Activation of Extracellular Ca(2+) Influx
title_full Salvia miltiorrhiza Induces Tonic Contraction of the Lower Esophageal Sphincter in Rats via Activation of Extracellular Ca(2+) Influx
title_fullStr Salvia miltiorrhiza Induces Tonic Contraction of the Lower Esophageal Sphincter in Rats via Activation of Extracellular Ca(2+) Influx
title_full_unstemmed Salvia miltiorrhiza Induces Tonic Contraction of the Lower Esophageal Sphincter in Rats via Activation of Extracellular Ca(2+) Influx
title_short Salvia miltiorrhiza Induces Tonic Contraction of the Lower Esophageal Sphincter in Rats via Activation of Extracellular Ca(2+) Influx
title_sort salvia miltiorrhiza induces tonic contraction of the lower esophageal sphincter in rats via activation of extracellular ca(2+) influx
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331792/
https://www.ncbi.nlm.nih.gov/pubmed/26270658
http://dx.doi.org/10.3390/molecules200814504
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