title: Pharmacological and biochemical study on the effects of selective phosphodiesterase inhibitors on human term myometrium.
abstract: This study was aimed at evaluating the in vitro effects of phosphodiesterase inhibitors and beta2-adrenoceptor agonists on spontaneous contractions of human term myometrium. Rolipram, RP 73401 (3-cyclopentyloxy-N-(3,5(-dichloro-4-pyridil)-4-methoxybenzamide) and Ro 20-1724 (1-4-(3-butoxy-4-methoxybenzyl)-2-imidozolidinone) (phosphodiesterase 4 inhibitors) inhibited spontaneous myometrial contractions (Emax approximately 100%; pD2 of 6.80+/-0.28, 6.84+/-0.32 and 6.31+/-0.03, respectively). Salbutamol and formoterol were less effective (Emax=40+/-6% and 35+/-12%, respectively) than phosphodiesterase 4 inhibitors to reduce myometrial contractility. Inhibitors of phosphodiesterase 3 (milrinone and siguazodan) and 5 (zaprinast) were marginally effective. Rolipram (10-30 nM) and siguazodan (0.1 microM) potentiated the response to salbutamol (Emax=75+/-12%, 88+/-8% and 73+/-12% and pD2=6.51+/-0.20, 6.93+/-0.29 and 6.48+/-0.16, respectively). Sodium nitroprusside (pD2=6.76+/-0.29) and theophylline (pD2=5.15+/-0.22) were effective inhibitors of myometrial contractions. Chromatographic separation of phosphodiesterase isoenzymes demonstrated that phosphodiesterase 4 is predominant but other phosphodiesterase isoenzymes were also identified. In conclusion, phosphodiesterase 4 inhibitors alone or combined with beta2-adrenoceptor agonists have potential interest as tocolytic agents.
authors.affiliation: Department of Pharmacology, Faculty of Medicine Paris-Ouest, Paris, France. Marc.Bardou@u-bourgogne.fr
authors.forename: M
authors.initials: M
authors.lastname: Bardou
authors.forename: J
authors.initials: J
authors.lastname: Cortijo
authors.forename: C
authors.initials: C
authors.lastname: Loustalot
authors.forename: S
authors.initials: S
authors.lastname: Taylor
authors.forename: A
authors.initials: A
authors.lastname: Perales-Marín
authors.forename: F J
authors.initials: FJ
authors.lastname: Mercier
authors.forename: M
authors.initials: M
authors.lastname: Dumas
authors.forename: C
authors.initials: C
authors.lastname: Deneux-Tharaux
authors.forename: R
authors.initials: R
authors.lastname: Frydman
authors.forename: E J
authors.initials: EJ
authors.lastname: Morcillo
authors.forename: C
authors.initials: C
authors.lastname: Advenier
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D002845:Chromatography; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000032:analysis*; D009215:Myometrium / Q000187:drug effects* / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000032:analysis*; D011247:Pregnancy
chemical_list: D000318:Adrenergic beta-Agonists; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D009599:Nitroprusside; D010727:Phosphoric Diester Hydrolases