Investigation of the role of the serotonergic activity of certain subtype-selective α1A antagonists in the relaxant effect on the pregnant rat uterus in vitro

Attila Mihályi, Eszter Ducza, R. Gáspár, G. Falkay

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Results from recent studies have shown that α1A-adrenergic receptor (α1A-AR) antagonists could offer a new alternative in the treatment of preterm delivery. However, members of this group [2-(2,6-dimethoxyphenoxyethyl aminomethyl-1,4-benzodioxane hydrochloride (WB4101), 5-methylurapidil (5-MU)] are known to influence serotonin (5-hydroxy-tryptamine) (5-HT1A) receptors, too. Our objective was to clarify the role of their 5-HT1A activities in the uterus relaxant effect. RT-PCR was used to determine mRNA expression of the receptor subtypes in 22 day pregnant rat uteri. Isolated uteri were stimulated by 5-HT or electrical field to investigate the contraction-inhibiting effect and the 5-HT1A activity of the α1A antagonists. Both receptor subtypes are present in rat myometrium. 5-HT induced contractions were inhibited by the α1A antagonists. Besides shifting the dose-response curve of 5-HT to the right, 5-MU decreased its maximal effect. The α1A antagonists inhibited electrical field stimulation-induced contractions. 5-HT1A blockade increased the maximal effect of 5-MU but did not change that of WB4101. These results suggest that the contraction increase caused by 5-HT is mediated by α1A receptors. Serotonergic activity of α1 antagonists and especially α1A antagonists should be investigated as it may alter their efficacy and could interfere with their side-effects. It is proposed that novel α1A antagonists should be designed with no 5-HT1A activity to achieve maximal relaxant effect.

Original languageEnglish
Pages (from-to)475-480
Number of pages6
JournalMolecular Human Reproduction
Volume9
Issue number7-8
Publication statusPublished - Jul 2003

Fingerprint

Uterus
Serotonin
Receptor, Serotonin, 5-HT1A
Adrenergic Antagonists
Myometrium
Electric Stimulation
In Vitro Techniques
Polymerase Chain Reaction
Messenger RNA
5-methylurapidil
(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane

Keywords

  • 5-HT1A receptors
  • Alpha1A-adrenoceptors
  • Rat
  • Tocolysis
  • Uterus

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Genetics
  • Developmental Biology
  • Embryology
  • Cell Biology

Cite this

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title = "Investigation of the role of the serotonergic activity of certain subtype-selective α1A antagonists in the relaxant effect on the pregnant rat uterus in vitro",
abstract = "Results from recent studies have shown that α1A-adrenergic receptor (α1A-AR) antagonists could offer a new alternative in the treatment of preterm delivery. However, members of this group [2-(2,6-dimethoxyphenoxyethyl aminomethyl-1,4-benzodioxane hydrochloride (WB4101), 5-methylurapidil (5-MU)] are known to influence serotonin (5-hydroxy-tryptamine) (5-HT1A) receptors, too. Our objective was to clarify the role of their 5-HT1A activities in the uterus relaxant effect. RT-PCR was used to determine mRNA expression of the receptor subtypes in 22 day pregnant rat uteri. Isolated uteri were stimulated by 5-HT or electrical field to investigate the contraction-inhibiting effect and the 5-HT1A activity of the α1A antagonists. Both receptor subtypes are present in rat myometrium. 5-HT induced contractions were inhibited by the α1A antagonists. Besides shifting the dose-response curve of 5-HT to the right, 5-MU decreased its maximal effect. The α1A antagonists inhibited electrical field stimulation-induced contractions. 5-HT1A blockade increased the maximal effect of 5-MU but did not change that of WB4101. These results suggest that the contraction increase caused by 5-HT is mediated by α1A receptors. Serotonergic activity of α1 antagonists and especially α1A antagonists should be investigated as it may alter their efficacy and could interfere with their side-effects. It is proposed that novel α1A antagonists should be designed with no 5-HT1A activity to achieve maximal relaxant effect.",
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AU - Falkay, G.

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