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Mechanism of Oxytocin-Induced Contraction in Rat Gastric Circular Smooth Muscle
Oxytocin produces an excitatory effect on gastric muscle through the activation of receptors present on stomach smooth muscle cells. However, the intracellular mechanisms that mediate oxytocin excitatory effects are still largely unknown. Therefore, we aimed to investigate the signaling pathways inv...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820280/ https://www.ncbi.nlm.nih.gov/pubmed/36613886 http://dx.doi.org/10.3390/ijms24010441 |
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author | Alqudah, Mohammad Razzaq, Rima Abdul Alfaqih, Mahmoud A. Al-Shboul, Othman Al-Dwairi, Ahmed Taha, Safa |
author_facet | Alqudah, Mohammad Razzaq, Rima Abdul Alfaqih, Mahmoud A. Al-Shboul, Othman Al-Dwairi, Ahmed Taha, Safa |
author_sort | Alqudah, Mohammad |
collection | PubMed |
description | Oxytocin produces an excitatory effect on gastric muscle through the activation of receptors present on stomach smooth muscle cells. However, the intracellular mechanisms that mediate oxytocin excitatory effects are still largely unknown. Therefore, we aimed to investigate the signaling pathways involved in oxytocin-induced contractions in gastric smooth muscle, shedding light on phospholipase C (PLC)-β1 signaling and its downstream molecules, including inositol 1,4,5- trisphosphate (IP(3)) and myosin light chain kinase (MLCK). The contractions of gastric smooth muscle from male rats were measured in an organ bath set up in response to exogenous oxytocin 10(−7) M, in the presence and absence of inhibitors of the indicated signaling molecules. Oxytocin (10(−9)–10(−5) M) induced dose-dependent stomach smooth muscle contraction. Pre-incubation with atosiban, an oxytocin receptor inhibitor, abolished the oxytocin-induced contraction. Moreover, PLC β1 inhibitor (U73122) and IP(3) inhibitor Xestospongin C inhibited oxytocin-induced muscle contraction to various degrees. Verapamil, a calcium channel blocker, inhibited oxytocin-induced contraction, and pre-incubation of the strips, with both verapamil and Xestospongin C, further inhibited the excitatory effect of oxytocin. Chelation of intracellular calcium with BAPT-AM (1,2-bis-(o-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid) significantly inhibited the effect of oxytocin on muscle contraction. Finally, pre-incubation of the strips with the Ca(2+)/calmodulin-dependent protein kinase selective inhibitor STO-609 significantly inhibited the contraction induced by oxytocin. These results suggest that oxytocin directly stimulates its cell surface receptor to activate PLC β1, which in turn liberates IP(3), which eventually elevates intracellular calcium, the prerequisite for smooth muscle contraction. |
format | Online Article Text |
id | pubmed-9820280 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98202802023-01-07 Mechanism of Oxytocin-Induced Contraction in Rat Gastric Circular Smooth Muscle Alqudah, Mohammad Razzaq, Rima Abdul Alfaqih, Mahmoud A. Al-Shboul, Othman Al-Dwairi, Ahmed Taha, Safa Int J Mol Sci Article Oxytocin produces an excitatory effect on gastric muscle through the activation of receptors present on stomach smooth muscle cells. However, the intracellular mechanisms that mediate oxytocin excitatory effects are still largely unknown. Therefore, we aimed to investigate the signaling pathways involved in oxytocin-induced contractions in gastric smooth muscle, shedding light on phospholipase C (PLC)-β1 signaling and its downstream molecules, including inositol 1,4,5- trisphosphate (IP(3)) and myosin light chain kinase (MLCK). The contractions of gastric smooth muscle from male rats were measured in an organ bath set up in response to exogenous oxytocin 10(−7) M, in the presence and absence of inhibitors of the indicated signaling molecules. Oxytocin (10(−9)–10(−5) M) induced dose-dependent stomach smooth muscle contraction. Pre-incubation with atosiban, an oxytocin receptor inhibitor, abolished the oxytocin-induced contraction. Moreover, PLC β1 inhibitor (U73122) and IP(3) inhibitor Xestospongin C inhibited oxytocin-induced muscle contraction to various degrees. Verapamil, a calcium channel blocker, inhibited oxytocin-induced contraction, and pre-incubation of the strips, with both verapamil and Xestospongin C, further inhibited the excitatory effect of oxytocin. Chelation of intracellular calcium with BAPT-AM (1,2-bis-(o-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid) significantly inhibited the effect of oxytocin on muscle contraction. Finally, pre-incubation of the strips with the Ca(2+)/calmodulin-dependent protein kinase selective inhibitor STO-609 significantly inhibited the contraction induced by oxytocin. These results suggest that oxytocin directly stimulates its cell surface receptor to activate PLC β1, which in turn liberates IP(3), which eventually elevates intracellular calcium, the prerequisite for smooth muscle contraction. MDPI 2022-12-27 /pmc/articles/PMC9820280/ /pubmed/36613886 http://dx.doi.org/10.3390/ijms24010441 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Alqudah, Mohammad Razzaq, Rima Abdul Alfaqih, Mahmoud A. Al-Shboul, Othman Al-Dwairi, Ahmed Taha, Safa Mechanism of Oxytocin-Induced Contraction in Rat Gastric Circular Smooth Muscle |
title | Mechanism of Oxytocin-Induced Contraction in Rat Gastric Circular Smooth Muscle |
title_full | Mechanism of Oxytocin-Induced Contraction in Rat Gastric Circular Smooth Muscle |
title_fullStr | Mechanism of Oxytocin-Induced Contraction in Rat Gastric Circular Smooth Muscle |
title_full_unstemmed | Mechanism of Oxytocin-Induced Contraction in Rat Gastric Circular Smooth Muscle |
title_short | Mechanism of Oxytocin-Induced Contraction in Rat Gastric Circular Smooth Muscle |
title_sort | mechanism of oxytocin-induced contraction in rat gastric circular smooth muscle |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820280/ https://www.ncbi.nlm.nih.gov/pubmed/36613886 http://dx.doi.org/10.3390/ijms24010441 |
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