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EFFECT OF α 1 ‐ADRENOCEPTOR SUBTYPE‐SELECTIVE INVERSE AGONISTS ON NON‐PREGNANT AND LATE‐PREGNANT CERVICAL RESISTANCE IN VITRO IN THE RAT
Author(s) -
KolarovszkiSipiczki Zoltán,
Gáspár Róbert,
Ducza Eszter,
Páldy Eszter,
Benyhe Sándor,
Borsodi Anna,
Falkay George
Publication year - 2007
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04529.x
Subject(s) - pertussis toxin , g protein , endocrinology , medicine , inverse agonist , gtp' , phenylephrine , in vitro , chemistry , western blot , receptor , agonist , biology , biochemistry , gene , enzyme , blood pressure
SUMMARY1 The aim of the present study was to compare and elucidate the effects of α 1 ‐adrenoceptor (α 1 ‐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 α 1 ‐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 α 1 ‐AR subtypes and the G‐protein‐activating effects of the inverse agonists were determined by reverse transcription–polymerase chain reaction, western blot and [ 35 S]‐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 α 1 ‐AR subtypes were increased on Day 18, but no further changes were observed after that. The [ 35 S]‐GTPγS binding studies revealed increased G‐protein activation of α 1A ‐AR and a moderate G‐protein activation of α 1B ‐ and α 1D ‐AR. The effect of WB 4101 to increase [ 35 S]‐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 α 1A ‐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 G i ‐protein. This effect of the α 1A ‐AR inverse agonist WB 4101 may offer a new therapeutic target in the prevention of premature labour.