Effects of the polyphenol resveratrol on contractility of human term pregnant myometrium

2015
Authors
Novaković, Radmila
Radunović, Nebojša
Marković-Lipkovski, Jasmina

Cirović, S.
Beleslin-Cokić, Bojana B.
Ilić, B.
Ivković, Branka

Heinle, Helmut
Živanović, Vladimir

Gojković-Bukarica, Ljiljana

Article (Published version)

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The ideal agent for prevention and treatment of uterine abnormal contractility has not been found. The polyphenol resveratrol possesses a wide spectrum of pharmacologic properties, but its influence on the contractility of human myometrium is not defined. The present study evaluated the effect of resveratrol on the oxytocin-induced contractions of human term pregnant myometrium in vitro and the contribution of different K+ channels to resveratrol action. Resveratrol induced a concentration-dependent relaxation of myometrium contractions (pD(2) value and maximal responses were 4.52 and 82.25%, respectively). Glibenclamide, a selective blocker of ATP-sensitive (K-ATP), iberiotoxin, a selective blockers of big-calcium sensitive (BKCa) and 4-aminopiridine, a non-selective blocker of voltage-sensitive (Kv) channels induced a significant shift to the right of the concentration-response curves of resveratrol. Inhibition achieved by 0.1 mM resveratrol was insensitive to all K+ channel blockers.... A K+ channel opener, pinacidil, inhibited oxytocin-induced contractions of pregnant myometrium with comparable potency and efficacy to resveratrol (pD(2) values and maximal relaxation were 4.52 and 83.67%, respectively). Based on K+ channel opener/blocker affinities, it appears that the inhibitory response of resveratrol involves different myometrial K+ channels. When applied in high concentrations, resveratrol has an additional K+-channel-independent mechanism(s) of action. Furthermore, immunohistochemistry staining and western blot analyses detected the presence and distribution of K-ATP, BKCa and Kv channel proteins in pregnant myometrium.
Keywords:
contraction / K+- channels / myometrium / pregnancy / resveratrolSource:
Molecular Human Reproduction, 2015, 21, 6, 545-551Publisher:
- Oxford Univ Press, Oxford
Funding / projects:
DOI: 10.1093/molehr/gav011
ISSN: 1360-9947
PubMed: 25750187
WoS: 000356261000006
Scopus: 2-s2.0-84942107911
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Institution/Community
PharmacyTY - JOUR AU - Novaković, Radmila AU - Radunović, Nebojša AU - Marković-Lipkovski, Jasmina AU - Cirović, S. AU - Beleslin-Cokić, Bojana B. AU - Ilić, B. AU - Ivković, Branka AU - Heinle, Helmut AU - Živanović, Vladimir AU - Gojković-Bukarica, Ljiljana PY - 2015 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2462 AB - The ideal agent for prevention and treatment of uterine abnormal contractility has not been found. The polyphenol resveratrol possesses a wide spectrum of pharmacologic properties, but its influence on the contractility of human myometrium is not defined. The present study evaluated the effect of resveratrol on the oxytocin-induced contractions of human term pregnant myometrium in vitro and the contribution of different K+ channels to resveratrol action. Resveratrol induced a concentration-dependent relaxation of myometrium contractions (pD(2) value and maximal responses were 4.52 and 82.25%, respectively). Glibenclamide, a selective blocker of ATP-sensitive (K-ATP), iberiotoxin, a selective blockers of big-calcium sensitive (BKCa) and 4-aminopiridine, a non-selective blocker of voltage-sensitive (Kv) channels induced a significant shift to the right of the concentration-response curves of resveratrol. Inhibition achieved by 0.1 mM resveratrol was insensitive to all K+ channel blockers. A K+ channel opener, pinacidil, inhibited oxytocin-induced contractions of pregnant myometrium with comparable potency and efficacy to resveratrol (pD(2) values and maximal relaxation were 4.52 and 83.67%, respectively). Based on K+ channel opener/blocker affinities, it appears that the inhibitory response of resveratrol involves different myometrial K+ channels. When applied in high concentrations, resveratrol has an additional K+-channel-independent mechanism(s) of action. Furthermore, immunohistochemistry staining and western blot analyses detected the presence and distribution of K-ATP, BKCa and Kv channel proteins in pregnant myometrium. PB - Oxford Univ Press, Oxford T2 - Molecular Human Reproduction T1 - Effects of the polyphenol resveratrol on contractility of human term pregnant myometrium VL - 21 IS - 6 SP - 545 EP - 551 DO - 10.1093/molehr/gav011 ER -
@article{ author = "Novaković, Radmila and Radunović, Nebojša and Marković-Lipkovski, Jasmina and Cirović, S. and Beleslin-Cokić, Bojana B. and Ilić, B. and Ivković, Branka and Heinle, Helmut and Živanović, Vladimir and Gojković-Bukarica, Ljiljana", year = "2015", abstract = "The ideal agent for prevention and treatment of uterine abnormal contractility has not been found. The polyphenol resveratrol possesses a wide spectrum of pharmacologic properties, but its influence on the contractility of human myometrium is not defined. The present study evaluated the effect of resveratrol on the oxytocin-induced contractions of human term pregnant myometrium in vitro and the contribution of different K+ channels to resveratrol action. Resveratrol induced a concentration-dependent relaxation of myometrium contractions (pD(2) value and maximal responses were 4.52 and 82.25%, respectively). Glibenclamide, a selective blocker of ATP-sensitive (K-ATP), iberiotoxin, a selective blockers of big-calcium sensitive (BKCa) and 4-aminopiridine, a non-selective blocker of voltage-sensitive (Kv) channels induced a significant shift to the right of the concentration-response curves of resveratrol. Inhibition achieved by 0.1 mM resveratrol was insensitive to all K+ channel blockers. A K+ channel opener, pinacidil, inhibited oxytocin-induced contractions of pregnant myometrium with comparable potency and efficacy to resveratrol (pD(2) values and maximal relaxation were 4.52 and 83.67%, respectively). Based on K+ channel opener/blocker affinities, it appears that the inhibitory response of resveratrol involves different myometrial K+ channels. When applied in high concentrations, resveratrol has an additional K+-channel-independent mechanism(s) of action. Furthermore, immunohistochemistry staining and western blot analyses detected the presence and distribution of K-ATP, BKCa and Kv channel proteins in pregnant myometrium.", publisher = "Oxford Univ Press, Oxford", journal = "Molecular Human Reproduction", title = "Effects of the polyphenol resveratrol on contractility of human term pregnant myometrium", volume = "21", number = "6", pages = "545-551", doi = "10.1093/molehr/gav011" }
Novaković, R., Radunović, N., Marković-Lipkovski, J., Cirović, S., Beleslin-Cokić, B. B., Ilić, B., Ivković, B., Heinle, H., Živanović, V.,& Gojković-Bukarica, L.. (2015). Effects of the polyphenol resveratrol on contractility of human term pregnant myometrium. in Molecular Human Reproduction Oxford Univ Press, Oxford., 21(6), 545-551. https://doi.org/10.1093/molehr/gav011
Novaković R, Radunović N, Marković-Lipkovski J, Cirović S, Beleslin-Cokić BB, Ilić B, Ivković B, Heinle H, Živanović V, Gojković-Bukarica L. Effects of the polyphenol resveratrol on contractility of human term pregnant myometrium. in Molecular Human Reproduction. 2015;21(6):545-551. doi:10.1093/molehr/gav011 .
Novaković, Radmila, Radunović, Nebojša, Marković-Lipkovski, Jasmina, Cirović, S., Beleslin-Cokić, Bojana B., Ilić, B., Ivković, Branka, Heinle, Helmut, Živanović, Vladimir, Gojković-Bukarica, Ljiljana, "Effects of the polyphenol resveratrol on contractility of human term pregnant myometrium" in Molecular Human Reproduction, 21, no. 6 (2015):545-551, https://doi.org/10.1093/molehr/gav011 . .