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Effects of Histamine on Cultured Interstitial Cells of Cajal in Murine Small Intestine
Interstitial cells of Cajal (ICCs) are the pacemaker cells in the gastrointestinal tract, and histamine is known to regulate neuronal activity, control vascular tone, alter endothelial permeability, and modulate gastric acid secretion. However, the action mechanisms of histamine in mouse small intes...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The Korean Physiological Society and The Korean Society of Pharmacology
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634092/ https://www.ncbi.nlm.nih.gov/pubmed/23626477 http://dx.doi.org/10.4196/kjpp.2013.17.2.149 |
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author | Kim, Byung Joo Kwon, Young Kyu Kim, Euiyong So, Insuk |
author_facet | Kim, Byung Joo Kwon, Young Kyu Kim, Euiyong So, Insuk |
author_sort | Kim, Byung Joo |
collection | PubMed |
description | Interstitial cells of Cajal (ICCs) are the pacemaker cells in the gastrointestinal tract, and histamine is known to regulate neuronal activity, control vascular tone, alter endothelial permeability, and modulate gastric acid secretion. However, the action mechanisms of histamine in mouse small intestinal ICCs have not been previously investigated, and thus, in the present study, we investigated the effects of histamine on mouse small intestinal ICCs, and sought to identify the receptors involved. Enzymatic digestions were used to dissociate ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record potentials (in current clamp mode) from cultured ICCs. Histamine was found to depolarize resting membrane potentials concentration dependently, and whereas 2-PEA (a selective H1 receptor agonist) induced membrane depolarizations, Dimaprit (a selective H2-agonist), R-alpha-methylhistamine (R-alpha-MeHa; a selective H3-agonist), and 4-methylhistamine (4-MH; a selective H4-agonist) did not. Pretreatment with Ca(2+)-free solution or thapsigargin (a Ca(2+)-ATPase inhibitor in endoplasmic reticulum) abolished the generation of pacemaker potentials and suppressed histamine-induced membrane depolarization. Furthermore, treatments with U-73122 (a phospholipase C inhibitor) or 5-fluoro-2-indolyl des-chlorohalopemide (FIPI; a phospholipase D inhibitor) blocked histamine-induced membrane depolarizations in ICCs. On the other hand, KT5720 (a protein kinase A inhibitor) did not block histamine-induced membrane depolarization. These results suggest that histamine modulates pacemaker potentials through H1 receptor-mediated pathways via external Ca(2+) influx and Ca(2+) release from internal stores in a PLC and PLD dependent manner. |
format | Online Article Text |
id | pubmed-3634092 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The Korean Physiological Society and The Korean Society of Pharmacology |
record_format | MEDLINE/PubMed |
spelling | pubmed-36340922013-04-26 Effects of Histamine on Cultured Interstitial Cells of Cajal in Murine Small Intestine Kim, Byung Joo Kwon, Young Kyu Kim, Euiyong So, Insuk Korean J Physiol Pharmacol Original Article Interstitial cells of Cajal (ICCs) are the pacemaker cells in the gastrointestinal tract, and histamine is known to regulate neuronal activity, control vascular tone, alter endothelial permeability, and modulate gastric acid secretion. However, the action mechanisms of histamine in mouse small intestinal ICCs have not been previously investigated, and thus, in the present study, we investigated the effects of histamine on mouse small intestinal ICCs, and sought to identify the receptors involved. Enzymatic digestions were used to dissociate ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record potentials (in current clamp mode) from cultured ICCs. Histamine was found to depolarize resting membrane potentials concentration dependently, and whereas 2-PEA (a selective H1 receptor agonist) induced membrane depolarizations, Dimaprit (a selective H2-agonist), R-alpha-methylhistamine (R-alpha-MeHa; a selective H3-agonist), and 4-methylhistamine (4-MH; a selective H4-agonist) did not. Pretreatment with Ca(2+)-free solution or thapsigargin (a Ca(2+)-ATPase inhibitor in endoplasmic reticulum) abolished the generation of pacemaker potentials and suppressed histamine-induced membrane depolarization. Furthermore, treatments with U-73122 (a phospholipase C inhibitor) or 5-fluoro-2-indolyl des-chlorohalopemide (FIPI; a phospholipase D inhibitor) blocked histamine-induced membrane depolarizations in ICCs. On the other hand, KT5720 (a protein kinase A inhibitor) did not block histamine-induced membrane depolarization. These results suggest that histamine modulates pacemaker potentials through H1 receptor-mediated pathways via external Ca(2+) influx and Ca(2+) release from internal stores in a PLC and PLD dependent manner. The Korean Physiological Society and The Korean Society of Pharmacology 2013-04 2013-04-10 /pmc/articles/PMC3634092/ /pubmed/23626477 http://dx.doi.org/10.4196/kjpp.2013.17.2.149 Text en Copyright © 2013 The Korean Physiological Society and The Korean Society of Pharmacology http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Kim, Byung Joo Kwon, Young Kyu Kim, Euiyong So, Insuk Effects of Histamine on Cultured Interstitial Cells of Cajal in Murine Small Intestine |
title | Effects of Histamine on Cultured Interstitial Cells of Cajal in Murine Small Intestine |
title_full | Effects of Histamine on Cultured Interstitial Cells of Cajal in Murine Small Intestine |
title_fullStr | Effects of Histamine on Cultured Interstitial Cells of Cajal in Murine Small Intestine |
title_full_unstemmed | Effects of Histamine on Cultured Interstitial Cells of Cajal in Murine Small Intestine |
title_short | Effects of Histamine on Cultured Interstitial Cells of Cajal in Murine Small Intestine |
title_sort | effects of histamine on cultured interstitial cells of cajal in murine small intestine |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634092/ https://www.ncbi.nlm.nih.gov/pubmed/23626477 http://dx.doi.org/10.4196/kjpp.2013.17.2.149 |
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