Radunović, Nebojša

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Wine polyphenol resveratrol inhibits contractions of isolated rat uterus by activation of smooth muscle inwardly rectifying potassium channels

Novaković, Radmila; Radunović, Nebojša; Rajković, Jovana; Đokić, Vladimir; Petrović, Aleksandar V.; Ivković, Branka; Ćupić, Vitomir; Kanjuh, Vladimir; Helmut, Heinlev; Gojković-Bukarica, Ljiljana

(Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd, 2016)

TY  - JOUR
AU  - Novaković, Radmila
AU  - Radunović, Nebojša
AU  - Rajković, Jovana
AU  - Đokić, Vladimir
AU  - Petrović, Aleksandar V.
AU  - Ivković, Branka
AU  - Ćupić, Vitomir
AU  - Kanjuh, Vladimir
AU  - Helmut, Heinlev
AU  - Gojković-Bukarica, Ljiljana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2769
AB  - Resveratrol is a phytoalexin produced in a number of plant species including grapes. The benefit of resveratrol to health is widely reported. Resveratrol has been found to promote relaxation of non-pregnant and pregnant uterus, but its mechanism of action is unclear. The aims of our study were to investigate the involvement of inwardly rectifying potassium channels (Kir) in inhibitory effects of resveratrol on three models of contractions of non-pregnant rat uterus: the spontaneous rhythmic contractions (SRC), oxytocin-elicited phasic contractions and tonic oxytocin-elicited contractions. Uterine strips were obtained from virgin female Wistar rats in oestrus. Strips were mounted into organ bath for recording isometric tension in Krebs-Ringer solution. Experiments followed a multiple curve design. In order to test the involvement of Kirchannels in a mechanism of action of resveratrol (1-100 μM),BaCl2 (1 mM),a antagonist of inwardly rectifying potassium channels was used. Resveratrol induced a concentration-dependent relaxation of all models of contractions. BaCl2 antagonized the response to resveratrolon SRC and oxytocin-elicited phasic contractions. Relaxation achieved by resveratrolon tonic oxytocin-elicited concentrations was insensitive to BaCl2.The antagonism of resveratrol effects by inwardly rectifying potassium channels antagonist suggests that Kir channels are involved in resveratrol action on phasic contractions of rat uterus. Inhibitory effect of resveratrol on tonic contractions did not include Kir channels.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Veterinarski glasnik
T1  - Wine polyphenol resveratrol inhibits contractions of isolated rat uterus by activation of smooth muscle inwardly rectifying potassium channels
VL  - 70
IS  - 3-4
SP  - 121
EP  - 129
DO  - 10.2298/VETGL1604121N
ER  - 
@article{
author = "Novaković, Radmila and Radunović, Nebojša and Rajković, Jovana and Đokić, Vladimir and Petrović, Aleksandar V. and Ivković, Branka and Ćupić, Vitomir and Kanjuh, Vladimir and Helmut, Heinlev and Gojković-Bukarica, Ljiljana",
year = "2016",
abstract = "Resveratrol is a phytoalexin produced in a number of plant species including grapes. The benefit of resveratrol to health is widely reported. Resveratrol has been found to promote relaxation of non-pregnant and pregnant uterus, but its mechanism of action is unclear. The aims of our study were to investigate the involvement of inwardly rectifying potassium channels (Kir) in inhibitory effects of resveratrol on three models of contractions of non-pregnant rat uterus: the spontaneous rhythmic contractions (SRC), oxytocin-elicited phasic contractions and tonic oxytocin-elicited contractions. Uterine strips were obtained from virgin female Wistar rats in oestrus. Strips were mounted into organ bath for recording isometric tension in Krebs-Ringer solution. Experiments followed a multiple curve design. In order to test the involvement of Kirchannels in a mechanism of action of resveratrol (1-100 μM),BaCl2 (1 mM),a antagonist of inwardly rectifying potassium channels was used. Resveratrol induced a concentration-dependent relaxation of all models of contractions. BaCl2 antagonized the response to resveratrolon SRC and oxytocin-elicited phasic contractions. Relaxation achieved by resveratrolon tonic oxytocin-elicited concentrations was insensitive to BaCl2.The antagonism of resveratrol effects by inwardly rectifying potassium channels antagonist suggests that Kir channels are involved in resveratrol action on phasic contractions of rat uterus. Inhibitory effect of resveratrol on tonic contractions did not include Kir channels.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Veterinarski glasnik",
title = "Wine polyphenol resveratrol inhibits contractions of isolated rat uterus by activation of smooth muscle inwardly rectifying potassium channels",
volume = "70",
number = "3-4",
pages = "121-129",
doi = "10.2298/VETGL1604121N"
}
Novaković, R., Radunović, N., Rajković, J., Đokić, V., Petrović, A. V., Ivković, B., Ćupić, V., Kanjuh, V., Helmut, H.,& Gojković-Bukarica, L.. (2016). Wine polyphenol resveratrol inhibits contractions of isolated rat uterus by activation of smooth muscle inwardly rectifying potassium channels. in Veterinarski glasnik
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 70(3-4), 121-129.
https://doi.org/10.2298/VETGL1604121N
Novaković R, Radunović N, Rajković J, Đokić V, Petrović AV, Ivković B, Ćupić V, Kanjuh V, Helmut H, Gojković-Bukarica L. Wine polyphenol resveratrol inhibits contractions of isolated rat uterus by activation of smooth muscle inwardly rectifying potassium channels. in Veterinarski glasnik. 2016;70(3-4):121-129.
doi:10.2298/VETGL1604121N .
Novaković, Radmila, Radunović, Nebojša, Rajković, Jovana, Đokić, Vladimir, Petrović, Aleksandar V., Ivković, Branka, Ćupić, Vitomir, Kanjuh, Vladimir, Helmut, Heinlev, Gojković-Bukarica, Ljiljana, "Wine polyphenol resveratrol inhibits contractions of isolated rat uterus by activation of smooth muscle inwardly rectifying potassium channels" in Veterinarski glasnik, 70, no. 3-4 (2016):121-129,
https://doi.org/10.2298/VETGL1604121N . .

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

Novaković, Radmila; Radunović, Nebojša; Marković-Lipkovski, Jasmina; Cirović, S.; Beleslin-Cokić, Bojana B.; Ilić, B.; Ivković, Branka; Heinle, Helmut; Živanović, Vladimir; Gojković-Bukarica, Ljiljana

(Oxford Univ Press, Oxford, 2015)

TY  - 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 . .
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