[Inhibition of uterine contractions: new in vitro pharmacological approaches on the pregnant human myometrium].
The aim of this study was to evaluate the in vitro effects of phosphodiesterase 4 inhibitors (PDE4I) and their combination with salbutamol (beta 2-adrenoceptor agonist) on spontaneous contractions and to investigate by in vitro and biochemical studies and analysis of mRNA expression the presence of beta 3-adrenoceptor in human near-term myometrium. Rolipram, RP 73401 and Ro 20-1724 (PDE4I) inhibited spontaneous myometrial contractions (Emax approximately 100 per cent; pD2 approximately 6.80 for the two first and 6.31 for Ro 20-1724). Rolipram 10(-8) M potentiated the response to salbutamol (Emax = 88 per cent vs. 40 per cent and pD2 = 6.93 and 6.36 with or without rolipram respectively). SR 59119A, a beta 3-adrenoceptor agonist, was more efficient than salbutamol in inhibiting the contractions (Emax 52 per cent and 27 per cent respectively, p < 0.05) but they both induced a significant increase of cAMP production. In both functional and biochemical studies, SR 59119A was only antagonized by the beta 3-adrenoceptor antagonist SR 59230A. The beta 3-AR mRNA was positively expressed in myometrium preparations in a reverse transcription polymerase chain assay. In conclusion, phosphodiesterase 4 inhibitors alone or combined with beta 2-adrenoceptor agonists and beta 3-adrenoceptor agonists might have potential interest as tocolytic agents.
Bardou
M
M
LPPCE, Faculté de Médecine, 7 bd Jeanne d'Arc, BP 87900, 21079 Dijon, France.
Loustalot
C
C
Simon
B
B
Morcillo
E
E
Croci
T
T
Advenier
C
C
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009215:Myometrium / Q000187:drug effects / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011247:Pregnancy / Q000502:physiology*; D011263:Pregnancy Trimester, Third; D011725:Pyridines / Q000494:pharmacology; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics; D020889:Rolipram / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014590:Uterine Contraction / Q000187:drug effects* / Q000502:physiology
D001549:Benzamides; D010726:Phosphodiesterase Inhibitors; D011725:Pyridines; D022702:Receptors, Adrenergic, beta-3; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D000242:Cyclic AMP; D020889:Rolipram; C087566:piclamilast