title: The Effects of p-nonylphenol on the Myometrial Contractile Activity.
abstract: We aimed to investigate the effects and mechanisms of action of p-nonylphenol(p-NP) on uterine contractility in rats. The uterine tissues of female Sprague Dawley rats in diestrus were bathed in isolated organ bath. The effects of vehicle alone (0.1% ethanol), the positive control 17-β-E2 (10(-5) M) and p-NP (10(-9) M, 10(-8) M, 10(-7) M, 10(-6) M) on spontaneous and KCl-induced uterine contractility of rats were studied. Also, the effects of p-NP in combination with actinomycin D (10(-5) M) (gene transcription inhibitor), cycloheximide (10(-4) M) (protein synthesis inhibitor), fulvestrant (10(-6) M) (pure estrogen receptor antagonist), 2-hydroxy-5-nonanoylbenzamide (10(-3) M) (compound 1b, anti-uterotrophic compound) on spontaneous uterine contractions, and with propranolol (20 µM) (β-adrenoceptor antagonist) and noradrenaline (5 µM) on KCl (40 mM) induced contractions were investigated. p-NP exhibited a concentration-dependent inhibition on spontaneous uterine contractions. There was no significant difference between the highest p-NP concentration (10(-6) M) and the positive control 17-β-E2 in terms of % inhibition (p>0.05). The inhibitory effect of p-NP (10(-6) M) on spontaneous contractions was blocked by actinomycin D (p<0.001), cycloheximide (p<0.001), fulvestrant (p<0.001) and compound 1b (p<0.001). 17-β-E2 (10(-5) M) exerted a higher inhibition % on KCl induced contractions than p-NP (10(-6) M). The relaxant effect of p-NP on KCl-induced uterine contractions was inhibited by noradrenaline (p<0.05) but not by propranolol (p>0.05). We suggest that p-NP inhibited uterine contractions similar as 17-β-E2 and genomic pathways are involved and β-adrenoceptors might modulate the activity of p-NP. In addition, compound 1b showed an uterotonic activity and reversed the effect of p-NP.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey.
authors.forename: F
authors.initials: F
authors.lastname: Yasemin Özatik
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Kaygısız
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey.
authors.forename: K
authors.initials: K
authors.lastname: Erol
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Ankara, Turkey.
authors.forename: Y
authors.initials: Y
authors.lastname: Dündar
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Ankara, Turkey.
authors.forename: T
authors.initials: T
authors.lastname: Önkol
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Eastern Mediterranean University, Turkey.
authors.forename: M F
authors.initials: MF
authors.lastname: Şahin
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D009638:Norepinephrine / Q000494:pharmacology; D010636:Phenols / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D015149:Tocolytic Agents / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects*
chemical_list: C000606942:2-hydroxy-5-nonanoylbenzamide; D001549:Benzamides; D010636:Phenols; D015149:Tocolytic Agents; D003609:Dactinomycin; D000077267:Fulvestrant; D004958:Estradiol; D011189:Potassium Chloride; C025256:nonylphenol; D003513:Cycloheximide; D011433:Propranolol; D009638:Norepinephrine