Cargando…
Mechanism of bombesin-induced tonic contraction of the porcine lower esophageal sphincter
Gastroesophageal reflux disease (GERD) is a disorder that is related to an incompetent lower esophageal sphincter (LES). Previous studies showed that bombesin could increase LES pressure in humans and opossums. The aim of the present study was to characterize the effects of bombesin on porcine LES c...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629149/ https://www.ncbi.nlm.nih.gov/pubmed/26522854 http://dx.doi.org/10.1038/srep15879 |
_version_ | 1782398539497734144 |
---|---|
author | Tsai, Ching-Chung Chang, Li-Ching Lin, Kai-Jen Tey, Shu-Leei Su, Yu-Tsun Liu, Ching-Wen Tsai, Tong-Rong Huang, Shih-Che |
author_facet | Tsai, Ching-Chung Chang, Li-Ching Lin, Kai-Jen Tey, Shu-Leei Su, Yu-Tsun Liu, Ching-Wen Tsai, Tong-Rong Huang, Shih-Che |
author_sort | Tsai, Ching-Chung |
collection | PubMed |
description | Gastroesophageal reflux disease (GERD) is a disorder that is related to an incompetent lower esophageal sphincter (LES). Previous studies showed that bombesin could increase LES pressure in humans and opossums. The aim of the present study was to characterize the effects of bombesin on porcine LES contraction. We used the selective agonists, neuromedin B (NMB), gastrin-releasing peptide (GRP), and [D-Tyr(6),Apa-4Cl(11),Phe(13),Nle(14)]bombesin-(6-14) (DTACPN-BN), as well as receptor antagonists of bombesin receptor subtype 2 (BB(2)), and 3 (BB(3)) for ex vivo contraction studies. Atropine, nifedipine, tetrodotoxin, and ω-conotoxin GVIA were used to explore the agonist-induced LES contraction mechanism. Reverse transcription polymerase chain reaction and immunohistochemistry were applied to detect bombesin receptor expression. Our results indicate that GRP and DTACPN-BN, but not NMB, induced tonic contractions of the porcine LES in a dose-dependent manner, and the contractions were inhibited with selective BB(2) and BB(3) antagonists. The GRP-induced contraction is mainly caused by L-type Ca(2+) channel-mediated Ca(2+) influx. However, DTACPN-BN-induced contractions are associated with neuronal conduction. RT-PCR and immunohistochemistry revealed that BB(2) and BB(3) were expressed in the porcine LES. Bombesin-induced tonic contraction of the LES is mediated through BB(2) and BB(3). Bombesin, BB(2,) and BB(3) agonists might have the potential to treat GERD. |
format | Online Article Text |
id | pubmed-4629149 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46291492015-11-05 Mechanism of bombesin-induced tonic contraction of the porcine lower esophageal sphincter Tsai, Ching-Chung Chang, Li-Ching Lin, Kai-Jen Tey, Shu-Leei Su, Yu-Tsun Liu, Ching-Wen Tsai, Tong-Rong Huang, Shih-Che Sci Rep Article Gastroesophageal reflux disease (GERD) is a disorder that is related to an incompetent lower esophageal sphincter (LES). Previous studies showed that bombesin could increase LES pressure in humans and opossums. The aim of the present study was to characterize the effects of bombesin on porcine LES contraction. We used the selective agonists, neuromedin B (NMB), gastrin-releasing peptide (GRP), and [D-Tyr(6),Apa-4Cl(11),Phe(13),Nle(14)]bombesin-(6-14) (DTACPN-BN), as well as receptor antagonists of bombesin receptor subtype 2 (BB(2)), and 3 (BB(3)) for ex vivo contraction studies. Atropine, nifedipine, tetrodotoxin, and ω-conotoxin GVIA were used to explore the agonist-induced LES contraction mechanism. Reverse transcription polymerase chain reaction and immunohistochemistry were applied to detect bombesin receptor expression. Our results indicate that GRP and DTACPN-BN, but not NMB, induced tonic contractions of the porcine LES in a dose-dependent manner, and the contractions were inhibited with selective BB(2) and BB(3) antagonists. The GRP-induced contraction is mainly caused by L-type Ca(2+) channel-mediated Ca(2+) influx. However, DTACPN-BN-induced contractions are associated with neuronal conduction. RT-PCR and immunohistochemistry revealed that BB(2) and BB(3) were expressed in the porcine LES. Bombesin-induced tonic contraction of the LES is mediated through BB(2) and BB(3). Bombesin, BB(2,) and BB(3) agonists might have the potential to treat GERD. Nature Publishing Group 2015-11-02 /pmc/articles/PMC4629149/ /pubmed/26522854 http://dx.doi.org/10.1038/srep15879 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Tsai, Ching-Chung Chang, Li-Ching Lin, Kai-Jen Tey, Shu-Leei Su, Yu-Tsun Liu, Ching-Wen Tsai, Tong-Rong Huang, Shih-Che Mechanism of bombesin-induced tonic contraction of the porcine lower esophageal sphincter |
title | Mechanism of bombesin-induced tonic contraction of the porcine lower esophageal sphincter |
title_full | Mechanism of bombesin-induced tonic contraction of the porcine lower esophageal sphincter |
title_fullStr | Mechanism of bombesin-induced tonic contraction of the porcine lower esophageal sphincter |
title_full_unstemmed | Mechanism of bombesin-induced tonic contraction of the porcine lower esophageal sphincter |
title_short | Mechanism of bombesin-induced tonic contraction of the porcine lower esophageal sphincter |
title_sort | mechanism of bombesin-induced tonic contraction of the porcine lower esophageal sphincter |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629149/ https://www.ncbi.nlm.nih.gov/pubmed/26522854 http://dx.doi.org/10.1038/srep15879 |
work_keys_str_mv | AT tsaichingchung mechanismofbombesininducedtoniccontractionoftheporcineloweresophagealsphincter AT changliching mechanismofbombesininducedtoniccontractionoftheporcineloweresophagealsphincter AT linkaijen mechanismofbombesininducedtoniccontractionoftheporcineloweresophagealsphincter AT teyshuleei mechanismofbombesininducedtoniccontractionoftheporcineloweresophagealsphincter AT suyutsun mechanismofbombesininducedtoniccontractionoftheporcineloweresophagealsphincter AT liuchingwen mechanismofbombesininducedtoniccontractionoftheporcineloweresophagealsphincter AT tsaitongrong mechanismofbombesininducedtoniccontractionoftheporcineloweresophagealsphincter AT huangshihche mechanismofbombesininducedtoniccontractionoftheporcineloweresophagealsphincter |