Original scientific paper
https://doi.org/10.3325/cmj.2016.57.100
The effects of estrogen on the α2-adrenergic receptor subtypes in rat uterine function in late pregnancy in vitro
Judit Hajagos-Tóth
; Department of Pharmacodynamics andBiopharmacy, Faculty of Pharmacy,University of Szeged, Szeged,Hungary
Judit Bóta
; Department of Pharmacodynamics andBiopharmacy, Faculty of Pharmacy,University of Szeged, Szeged,Hungary
Eszter Ducza
; Department of Pharmacodynamics andBiopharmacy, Faculty of Pharmacy,University of Szeged, Szeged,Hungary
Adrienn Csányi
; Department of Pharmacodynamics andBiopharmacy, Faculty of Pharmacy,University of Szeged, Szeged,Hungary
Zita Tiszai
; Department of Pharmacodynamics andBiopharmacy, Faculty of Pharmacy,University of Szeged, Szeged,Hungary
Anna Borsodi
; Institute of Biochemistry, Biological Research Centre, HungarianAcademy of Sciences, Szeged, Hungary
Reza Samavati
; Institute of Biochemistry, Biological Research Centre, HungarianAcademy of Sciences, Szeged, Hungary
Sándor Benyhe
; Institute of Biochemistry, Biological Research Centre, HungarianAcademy of Sciences, Szeged, Hungary
Róbert Gáspár
orcid.org/0000-0002-1571-7579
; Department of Pharmacodynamics andBiopharmacy, Faculty of Pharmacy,University of Szeged, Szeged,Hungary
Abstract
Aim To assess the effect of 17β-estradiol pretreatment on
the function and expression of α2- adrenergic receptors
(ARs) subtypes in late pregnancy in rats.
Methods Sprague-Dawley rats (n = 37) were treated with
17β-estradiol for 4 days starting from the 18th day of pregnancy.
The myometrial expression of the α2-AR subtypes
was determined by real time polymerase chain reaction
and Western blot analysis. In vitro contractions were stimulated
with (-)-noradrenaline, and its effect was modified
with the selective antagonists BRL 44408 (α2A), ARC 239
(α2B/C), and spiroxatrine (α2A). The cyclic adenosine monophosphate
(cAMP) accumulation was also measured. The
activated G-protein level was investigated by guanosine
5’-O-[gamma-thio]triphosphate (GTPγS) binding assay.
Results 17β-estradiol pretreatment decreased the contractile
effect of (-)-noradrenaline via the α2-ARs, and abolished
the contractile effect via the α2B-ARs. All the α2-AR
subtypes’ mRNA was significantly decreased. 17β-estradiol
pretreatment significantly increased the myometrial cAMP
level in the presence of BRL 44408 (P = 0.001), ARC 239
(P = 0.007), and spiroxatrine (P = 0.045), but did not modify
it in the presence of spiroxatrine + BRL 44408 combination
(P = 0.073). It also inhibited the G-protein-activating effect
of (-)-noradrenaline by 25% in the presence of BRL 44408 +
spiroxatrine combination.
Conclusions The expression of the α2-AR subtypes is sensitive
to 17β-estradiol, which decreases the contractile response
of (-)-noradrenaline via the α2B-AR subtype, and
might cause changes in G-protein signaling pathway. Estrogen
dysregulation may be responsible for preterm labor
or uterine inertia via the α2-ARs
Keywords
Hrčak ID:
169470
URI
Publication date:
15.4.2016.
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