Resveratrol Relaxes Human Gastric Smooth Muscles Through High Conductance Calcium-Activated Potassium Channel in a Nitric Oxide-independent Manner

Resveratrol, as a polyphenolic compound that can be isolated from plants, and also a component of red wine has broad beneficial pharmacological properties. The aim was to investigate the role of nitric oxide and potassium channels in resveratrol-induced relaxation of human gastric smooth muscle. Gas...

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Main Authors: Beata Modzelewska, Krzysztof Drygalski, Hady Razak Hady, Aleksandra Kiełczewska, Andrzej Chomentowski, Krzysztof Koryciński, Paulina Głuszyńska, Tomasz Kleszczewski
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-01-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.823887/full
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author Beata Modzelewska
Krzysztof Drygalski
Krzysztof Drygalski
Hady Razak Hady
Aleksandra Kiełczewska
Andrzej Chomentowski
Krzysztof Koryciński
Paulina Głuszyńska
Tomasz Kleszczewski
author_facet Beata Modzelewska
Krzysztof Drygalski
Krzysztof Drygalski
Hady Razak Hady
Aleksandra Kiełczewska
Andrzej Chomentowski
Krzysztof Koryciński
Paulina Głuszyńska
Tomasz Kleszczewski
author_sort Beata Modzelewska
collection DOAJ
description Resveratrol, as a polyphenolic compound that can be isolated from plants, and also a component of red wine has broad beneficial pharmacological properties. The aim was to investigate the role of nitric oxide and potassium channels in resveratrol-induced relaxation of human gastric smooth muscle. Gastric tissues were obtained from patients who underwent sleeve gastrectomy for severe obesity (n = 10 aged 21–48; BMI 48.21 ± 1.14). The mechanical activity from the muscle strips was detected under isometric conditions as the response to increasing concentrations of resveratrol before and after different pharmacological treatments. Resveratrol caused an observable, dose-dependent gastric muscle relaxation. The maximal response caused by the highest concentration of resveratrol was 83.49 ± 2.85% (p < 0.0001) of the control. Preincubation with L-NNA, L-NAME, or ODQ did not prevent the resveratrol-induced relaxation. Apamin, glibenclamide, 4AP or tamoxifen, did not inhibit the relaxing effect of resveratrol, as well. In turn, blocking BKCa by TEA, iberiotoxin, or charybdotoxin resulted in inhibition of resveratrol-induced relaxation (91.08 ± 2.07, p < 0.05; 95.60 ± 1.52, p < 0.01 and 89.58 ± 1.98, p < 0.05, respectively). This study provides the first observation that the relaxant effects of resveratrol in human gastric muscle strips occur directly through BKCa channels and independently of nitric oxide signaling pathways. Furthermore, there is considerable potential for further extensive clinical studies with resveratrol as an effective new drug or health supplement to treat gastrointestinal dyspepsia and other gastric hypermotility disorders.
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spelling doaj.art-66990ba2718547afa5853365bb3f36f52022-12-22T04:09:33ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-01-011310.3389/fphar.2022.823887823887Resveratrol Relaxes Human Gastric Smooth Muscles Through High Conductance Calcium-Activated Potassium Channel in a Nitric Oxide-independent MannerBeata Modzelewska0Krzysztof Drygalski1Krzysztof Drygalski2Hady Razak Hady3Aleksandra Kiełczewska4Andrzej Chomentowski5Krzysztof Koryciński6Paulina Głuszyńska7Tomasz Kleszczewski8Department of Biophysics, Faculty of Medicine, Medical University of Bialystok, Bialystok, PolandDepartment of Biophysics, Faculty of Medicine, Medical University of Bialystok, Bialystok, PolandClinical Research Center, Medical University of Bialystok, Bialystok, PolandClinical Department of General and Endocrine Surgery, Medical University of Bialystok, Bialystok, PolandDepartment of Biophysics, Faculty of Medicine, Medical University of Bialystok, Bialystok, PolandDepartment of Biophysics, Faculty of Medicine, Medical University of Bialystok, Bialystok, PolandDepartment of Biophysics, Faculty of Medicine, Medical University of Bialystok, Bialystok, PolandClinical Department of General and Endocrine Surgery, Medical University of Bialystok, Bialystok, PolandDepartment of Biophysics, Faculty of Medicine, Medical University of Bialystok, Bialystok, PolandResveratrol, as a polyphenolic compound that can be isolated from plants, and also a component of red wine has broad beneficial pharmacological properties. The aim was to investigate the role of nitric oxide and potassium channels in resveratrol-induced relaxation of human gastric smooth muscle. Gastric tissues were obtained from patients who underwent sleeve gastrectomy for severe obesity (n = 10 aged 21–48; BMI 48.21 ± 1.14). The mechanical activity from the muscle strips was detected under isometric conditions as the response to increasing concentrations of resveratrol before and after different pharmacological treatments. Resveratrol caused an observable, dose-dependent gastric muscle relaxation. The maximal response caused by the highest concentration of resveratrol was 83.49 ± 2.85% (p < 0.0001) of the control. Preincubation with L-NNA, L-NAME, or ODQ did not prevent the resveratrol-induced relaxation. Apamin, glibenclamide, 4AP or tamoxifen, did not inhibit the relaxing effect of resveratrol, as well. In turn, blocking BKCa by TEA, iberiotoxin, or charybdotoxin resulted in inhibition of resveratrol-induced relaxation (91.08 ± 2.07, p < 0.05; 95.60 ± 1.52, p < 0.01 and 89.58 ± 1.98, p < 0.05, respectively). This study provides the first observation that the relaxant effects of resveratrol in human gastric muscle strips occur directly through BKCa channels and independently of nitric oxide signaling pathways. Furthermore, there is considerable potential for further extensive clinical studies with resveratrol as an effective new drug or health supplement to treat gastrointestinal dyspepsia and other gastric hypermotility disorders.https://www.frontiersin.org/articles/10.3389/fphar.2022.823887/fullresveratrolsmooth musclesgastric motilitypotassium channelsnitric oxide
spellingShingle Beata Modzelewska
Krzysztof Drygalski
Krzysztof Drygalski
Hady Razak Hady
Aleksandra Kiełczewska
Andrzej Chomentowski
Krzysztof Koryciński
Paulina Głuszyńska
Tomasz Kleszczewski
Resveratrol Relaxes Human Gastric Smooth Muscles Through High Conductance Calcium-Activated Potassium Channel in a Nitric Oxide-independent Manner
Frontiers in Pharmacology
resveratrol
smooth muscles
gastric motility
potassium channels
nitric oxide
title Resveratrol Relaxes Human Gastric Smooth Muscles Through High Conductance Calcium-Activated Potassium Channel in a Nitric Oxide-independent Manner
title_full Resveratrol Relaxes Human Gastric Smooth Muscles Through High Conductance Calcium-Activated Potassium Channel in a Nitric Oxide-independent Manner
title_fullStr Resveratrol Relaxes Human Gastric Smooth Muscles Through High Conductance Calcium-Activated Potassium Channel in a Nitric Oxide-independent Manner
title_full_unstemmed Resveratrol Relaxes Human Gastric Smooth Muscles Through High Conductance Calcium-Activated Potassium Channel in a Nitric Oxide-independent Manner
title_short Resveratrol Relaxes Human Gastric Smooth Muscles Through High Conductance Calcium-Activated Potassium Channel in a Nitric Oxide-independent Manner
title_sort resveratrol relaxes human gastric smooth muscles through high conductance calcium activated potassium channel in a nitric oxide independent manner
topic resveratrol
smooth muscles
gastric motility
potassium channels
nitric oxide
url https://www.frontiersin.org/articles/10.3389/fphar.2022.823887/full
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