Different roles of α₂-adrenoceptor subtypes in non-pregnant and late-pregnant uterine contractility in vitro in the rat

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• 作者：Ró ; bert Gá ; spá ; r ; Adrienn Gá ; l ; Má ; rta Gá ; lik ; Eszter Ducza ; Rená ; ta Minorics ; Zoltá ; n Kolarovszki-Sipiczki ; Anna Klukovits ; George Falkay
• 关键词：α ; ₂-Adrenoceptors ; Rat ; Subtype-selective antagonists ; Pregnancy ; Uterus ; cAMP ; Premature labour
• 刊名：Neurochemistry International
• 出版年：2007
• 出版时间：October 2007
• 年：2007
• 卷：51
• 期：5
• 页码：311-318
• 全文大小：834 K

文摘

The roles of the α₂-adrenoceptor (α₂-AR) subtypes (α_2A-, α_2B- and α_2C-AR) in uterine contractility have not been investigated. The aims of this study were to identify these receptors in the non-pregnant and the late-pregnant rat myometrium and to determine their roles in contractions. We found that the myometrial α₂-AR subtypes are involved differently in the control of late-pregnant contractions, while they have no influence on the contractions of the non-pregnant myometrium.

The myometrial expressions of the α₂-AR subtypes were determined by RT-PCR and Western blotting techniques. In vitro contractions were stimulated with noradrenaline, and its effect was modified with the selective antagonists BRL 44408 (α_2A), ARC 239 (α_2B/C) and spiroxatrine (α_2C). cAMP production was followed by noradrenaline stimulation in the presence of isobutylmethylxanthine and forskolin, and alterations induced in it by the antagonists were determined with an Enzyme Immunoassay Kit. The most effective antagonist was tested on labour-induced uteri in vitro.

All the α₂-AR subtypes were identified in both non-pregnant and pregnant uteri. Noradrenaline was not able to contract the non-pregnant tissue in the presence of propranolol and doxazosin, while its contracting effect in the pregnant uteri was enhanced by BRL 44408, spiroxatrine and the combination BRL 44408 + spiroxatrine. ARC 239 exerted a strong inhibitory effect on noradrenaline-stimulated contractions. The increasing and the decreasing effects of the compounds were confirmed by the changes in the intracellular cAMP levels. The effect of ARC 239 on the labour-induced myometrium was similar to that on the 22-day-pregnant myometrium.

The stimulation of α₂-ARs does not evoke contractions in the non-pregnant uterus. The α_2A- and α_2C-ARs mediate decreases, while the α_2B-AR mediates an increase in the contractions in the 22-day-pregnant myometrium. These differences may offer new targets for drugs against premature contractions in pregnancy.