Effects of the polyphenol resveratrol on contractility of human term pregnant myometrium.
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 (pD2 value and maximal responses were 4.52 and 82.25%, respectively). Glibenclamide, a selective blocker of ATP-sensitive (KATP), iberiotoxin, a selective blockers of big-calcium sensitive (BK(Ca)) 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 (pD2 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 KATP, BK(Ca) and Kv channel proteins in pregnant myometrium.
Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
R
R
Novaković
Institute of Gynecology and Obstetrics, Clinical Center of Serbia, 11000 Belgrade, Serbia.
N
N
Radunović
Institute of Pathology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
J
J
Marković-Lipkovski
Institute of Pathology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
S
S
Ćirović
Clinic of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia.
B
B
Beleslin-Čokić
Clinic of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia.
B
B
Ilić
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia.
B
B
Ivković
Institute of Physiology, University of Tuebingen, 72072 Tuebingen, Germany.
H
H
Heinle
University Hospital Center 'Dr Dragiša Mišović-Dedinje', 11000 Belgrade, Serbia.
V
V
Živanović
Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia l.g.bukarica@sezampro.rs.
L J
LJ
Gojković-Bukarica
D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009215:Myometrium / Q000187:drug effects*; D010121:Oxytocin / Q000494:pharmacology; D020110:Pinacidil / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism; D011247:Pregnancy; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*
D015221:Potassium Channels; D013267:Stilbenes; D010121:Oxytocin; D020110:Pinacidil; D000077185:Resveratrol
K+- channels; contraction; myometrium; pregnancy; resveratrol