[Pharmacological models to investigate the role of the adrenergic system on post-partum rat uterus].
The adrenergic system plays a major role in the regulation of the pregnant uterine contractility. Our aim was to develop an experimental animal model to study the role of the alpha 1A-adrenergic receptor (AR) in uterine motor activity by antisense oligonucleotides (AONs). AONs were injected with DOTAP and pluronic gel into the uterine lumen of post-partum rats 2-3 hours after delivery. The decrease of the alpha 1A-AR density by AON was demonstrated by RT-PCR method, Western blot analysis and radioligand binding assay on rat uterus preparations 24 h after delivery. The changes in the contractility of the uterus were measured on isolated rat uterine tissue by electric field stimulation (EFS). The EFS investigation demonstrated that the effect of the specific alpha 1A-blocker 5-methylurapidil and WB4101 was significantly decreased in the AON-treated rat uterus as compared to the control group but the effect of the beta-mimetic terbutalin and alpha 1D-antagonist BMY7378 was unchanged. Our result suggest that the alpha 1A-ARs play a very important role in the regulation of uterine contractility, and may serve as the basis for a subsequent new group of tocolytics (uterus selective alpha 1-antagonists), which may lead to more selective therapy than currently used beta-mimetics.
Ducza
E
E
Szegedi Tudományegyetem, Gyógyszerhatástani és Biofarmáciai Intézet, Szeged.
Gáspár
R
R
Márki
A
A
Bottka
S
S
Falkay
G
G
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D036861:Delivery, Obstetric; D004146:Dioxanes / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D007774:Lactation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014590:Uterine Contraction / Q000502:physiology; D014599:Uterus / Q000187:drug effects / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D018340:Receptors, Adrenergic, alpha-1; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane