title: Influence of the formamidine pesticide amitraz and its metabolites on porcine myometrial contractility: involvement of alpha 2-adrenoceptors and Ca2+ channels.
abstract: Isolated uterine strips were used to study the effects of amitraz and its metabolites on porcine myometrial contractility during the luteal phase of the estrous cycle. Amitraz and its active metabolite BTS27271 (10(-8)-10(-5) M) caused a dose-dependent increase in myometrial contractility in the luteal phase strips, and BTS27271 was more efficacious than amitraz in this aspect. The other metabolites of amitraz at < or = 10(-4) M did not affect porcine myometrial contractility. The alpha 2-adrenoceptor antagonist, yohimbine (10(-8) -3 x 10(-7) M), but not the alpha 1-adrenoceptor antagonist, prazosin (10(-6) M), blocked the effect of amitraz and BTS27271 in a dose-dependent manner. When uterine strips were pretreated with the Ca(2+)-free Tyrode's solution or the voltage-dependent Ca2+ channel blocker verapamil (3 x 10(-5) M), the contractile effects of amitraz and BTS27271 were completely abolished, whereas those of carbachol were reduced. The results suggested that the amitraz- and BTS27271-induced myometrial contractions are mediated by alpha 2-adrenoceptors and this effect is mediated by an increase in extracellular Ca2+ influx through voltage-dependent Ca2+ channels.
authors.affiliation: Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50011.
authors.forename: D H
authors.initials: DH
authors.lastname: Shin
authors.forename: W H
authors.initials: WH
authors.lastname: Hsu
mesh_terms: D000578:Amidines / Q000633:toxicity; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007306:Insecticides / Q000633:toxicity*; D008183:Luteal Phase; D009215:Myometrium / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D014052:Toluidines / Q000037:antagonists & inhibitors / Q000633:toxicity*; D014590:Uterine Contraction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000578:Amidines; D015220:Calcium Channels; D007306:Insecticides; D018341:Receptors, Adrenergic, alpha-2; D014052:Toluidines; D015016:Yohimbine; C025699:U 40481; C014983:amitraz; D002217:Carbachol; D014700:Verapamil; D002118:Calcium; D011224:Prazosin