Effect of α1-adrenoceptor subtype-selective inverse agonists on non-pregnant and late-pregnant cervical resistance in vitro in the rat

Zoltán Kolarovszki-Sipiczki, R. Gáspár, Eszter Ducza, Eszter Páldy, S. Benyhe, A. Borsodi, G. Falkay

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

1. The aim of the present study was to compare and elucidate the effects of α1-adrenoceptor (α1-AR) subtype-selective inverse agonists on non-pregnant and late-pregnant rat cervical tone. 2. Cervical resistance was investigated in in vitro stretching tests in the absence or presence of α1-AR subtype-selective inverse agonists (WB 4101, AH 11110A and BMY 7378; all at 10-6 mol/L), whereas the mRNA levels and density of the α1-AR subtypes and the G-protein-activating effects of the inverse agonists were determined by reverse transcription-polymerase chain reaction, western blot and [35S]-GTPγS binding techniques, respectively. 3. The inverse agonists did not cause any change in resistance in non-pregnant and 18-day-pregnant samples. WB 4101 increased cervical resistance from Day 20, whereas AH 11110A had no effect and BMY 7378 exhibited such an action only on Day 21. Phenylephrine (10-4 mol/L) had no effect on cervical resistance on Day 22. The mRNA levels and density of all α1-AR subtypes were increased on Day 18, but no further changes were observed after that. The [35S]-GTPγS binding studies revealed increased G-protein activation of α1A-AR and a moderate G-protein activation of α1B- and α1D-AR. The effect of WB 4101 to increase [35S]-GTPγS binding was blocked by pertussis toxin (50 ng/mL). Phenylephrine caused a slight and significant decrease in the amount of activated G-protein on Day 22. 4. The effects of inverse agonists on the α1A-AR can enhance cervical resistance in the late-pregnant rat in vitro. This action is mediated, at least in part, by a pertussis toxin-sensitive Gi-protein. This effect of the α1A- AR inverse agonist WB 4101 may offer a new therapeutic target in the prevention of premature labour.

Original languageEnglish
Pages (from-to)42-47
Number of pages6
JournalClinical and Experimental Pharmacology and Physiology
Volume34
Issue number1-2
DOIs
Publication statusPublished - Jan 2007

Fingerprint

GTP-Binding Proteins
Adrenergic Receptors
Pertussis Toxin
Phenylephrine
Messenger RNA
Premature Obstetric Labor
Reverse Transcription
Western Blotting
Polymerase Chain Reaction
(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane
In Vitro Techniques
Proteins
AH 11110A
BMY 7378
Therapeutics

Keywords

  • α- adrenoceptor subtypes
  • α-adrenoceptor inverse agonists
  • [S]- GTPγS binding
  • Cervical resistance
  • Cervical ripening
  • G -protein
  • Pertussis toxin
  • Premature labour

ASJC Scopus subject areas

  • Physiology
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

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title = "Effect of α1-adrenoceptor subtype-selective inverse agonists on non-pregnant and late-pregnant cervical resistance in vitro in the rat",
abstract = "1. The aim of the present study was to compare and elucidate the effects of α1-adrenoceptor (α1-AR) subtype-selective inverse agonists on non-pregnant and late-pregnant rat cervical tone. 2. Cervical resistance was investigated in in vitro stretching tests in the absence or presence of α1-AR subtype-selective inverse agonists (WB 4101, AH 11110A and BMY 7378; all at 10-6 mol/L), whereas the mRNA levels and density of the α1-AR subtypes and the G-protein-activating effects of the inverse agonists were determined by reverse transcription-polymerase chain reaction, western blot and [35S]-GTPγS binding techniques, respectively. 3. The inverse agonists did not cause any change in resistance in non-pregnant and 18-day-pregnant samples. WB 4101 increased cervical resistance from Day 20, whereas AH 11110A had no effect and BMY 7378 exhibited such an action only on Day 21. Phenylephrine (10-4 mol/L) had no effect on cervical resistance on Day 22. The mRNA levels and density of all α1-AR subtypes were increased on Day 18, but no further changes were observed after that. The [35S]-GTPγS binding studies revealed increased G-protein activation of α1A-AR and a moderate G-protein activation of α1B- and α1D-AR. The effect of WB 4101 to increase [35S]-GTPγS binding was blocked by pertussis toxin (50 ng/mL). Phenylephrine caused a slight and significant decrease in the amount of activated G-protein on Day 22. 4. The effects of inverse agonists on the α1A-AR can enhance cervical resistance in the late-pregnant rat in vitro. This action is mediated, at least in part, by a pertussis toxin-sensitive Gi-protein. This effect of the α1A- AR inverse agonist WB 4101 may offer a new therapeutic target in the prevention of premature labour.",
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T1 - Effect of α1-adrenoceptor subtype-selective inverse agonists on non-pregnant and late-pregnant cervical resistance in vitro in the rat

AU - Kolarovszki-Sipiczki, Zoltán

AU - Gáspár, R.

AU - Ducza, Eszter

AU - Páldy, Eszter

AU - Benyhe, S.

AU - Borsodi, A.

AU - Falkay, G.

PY - 2007/1

Y1 - 2007/1

N2 - 1. The aim of the present study was to compare and elucidate the effects of α1-adrenoceptor (α1-AR) subtype-selective inverse agonists on non-pregnant and late-pregnant rat cervical tone. 2. Cervical resistance was investigated in in vitro stretching tests in the absence or presence of α1-AR subtype-selective inverse agonists (WB 4101, AH 11110A and BMY 7378; all at 10-6 mol/L), whereas the mRNA levels and density of the α1-AR subtypes and the G-protein-activating effects of the inverse agonists were determined by reverse transcription-polymerase chain reaction, western blot and [35S]-GTPγS binding techniques, respectively. 3. The inverse agonists did not cause any change in resistance in non-pregnant and 18-day-pregnant samples. WB 4101 increased cervical resistance from Day 20, whereas AH 11110A had no effect and BMY 7378 exhibited such an action only on Day 21. Phenylephrine (10-4 mol/L) had no effect on cervical resistance on Day 22. The mRNA levels and density of all α1-AR subtypes were increased on Day 18, but no further changes were observed after that. The [35S]-GTPγS binding studies revealed increased G-protein activation of α1A-AR and a moderate G-protein activation of α1B- and α1D-AR. The effect of WB 4101 to increase [35S]-GTPγS binding was blocked by pertussis toxin (50 ng/mL). Phenylephrine caused a slight and significant decrease in the amount of activated G-protein on Day 22. 4. The effects of inverse agonists on the α1A-AR can enhance cervical resistance in the late-pregnant rat in vitro. This action is mediated, at least in part, by a pertussis toxin-sensitive Gi-protein. This effect of the α1A- AR inverse agonist WB 4101 may offer a new therapeutic target in the prevention of premature labour.

AB - 1. The aim of the present study was to compare and elucidate the effects of α1-adrenoceptor (α1-AR) subtype-selective inverse agonists on non-pregnant and late-pregnant rat cervical tone. 2. Cervical resistance was investigated in in vitro stretching tests in the absence or presence of α1-AR subtype-selective inverse agonists (WB 4101, AH 11110A and BMY 7378; all at 10-6 mol/L), whereas the mRNA levels and density of the α1-AR subtypes and the G-protein-activating effects of the inverse agonists were determined by reverse transcription-polymerase chain reaction, western blot and [35S]-GTPγS binding techniques, respectively. 3. The inverse agonists did not cause any change in resistance in non-pregnant and 18-day-pregnant samples. WB 4101 increased cervical resistance from Day 20, whereas AH 11110A had no effect and BMY 7378 exhibited such an action only on Day 21. Phenylephrine (10-4 mol/L) had no effect on cervical resistance on Day 22. The mRNA levels and density of all α1-AR subtypes were increased on Day 18, but no further changes were observed after that. The [35S]-GTPγS binding studies revealed increased G-protein activation of α1A-AR and a moderate G-protein activation of α1B- and α1D-AR. The effect of WB 4101 to increase [35S]-GTPγS binding was blocked by pertussis toxin (50 ng/mL). Phenylephrine caused a slight and significant decrease in the amount of activated G-protein on Day 22. 4. The effects of inverse agonists on the α1A-AR can enhance cervical resistance in the late-pregnant rat in vitro. This action is mediated, at least in part, by a pertussis toxin-sensitive Gi-protein. This effect of the α1A- AR inverse agonist WB 4101 may offer a new therapeutic target in the prevention of premature labour.

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KW - α-adrenoceptor inverse agonists

KW - [S]- GTPγS binding

KW - Cervical resistance

KW - Cervical ripening

KW - G -protein

KW - Pertussis toxin

KW - Premature labour

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