Pharmacological and biochemical study on the effects of selective phosphodiesterase inhibitors on human term myometrium

This study was aimed at evaluating the in vitro effects of phosphodiesteras e inhibitors and beta(2)-adrenoceptor agonists on spontaneous contractions of human term myometrium. Rolipram, RP 73401 (3-cyclopentyloxy-N-(3,5(-dich loro-4-pyridil)-4-methoxybenzamide) and Ro 20-1724 ( 1-4-(3-butoxy-4-methox ybenzyl)-2-imidozolidinone) none) (phosphodiesterase 4 inhibitors) inhibite d spontaneous myometrial contractions (E-max similar to 100%; pD(2) of 6.80 +/- 10.28, 6.84 +/- 0.32 and 6.31 +/- 0.03, respectively). Salbutamol and formoterol were less effective (E-max = 40 +/- 6% and 35 +/- 12%, respectiv ely) than phosphodiesterase 4 inhibitors to reduce myometrial contractility . Inhibitors of phosphodiesterase 3 (milrinone and siguazodan) and 5 (zapri nast) were marginally effective. Rolipram (10-30 nM) and siguazodan (0.1 mu M) potentiated the response to salbutamol (E-max = 75 +/- 12%, 88 +/- 8% a nd 73 +/- 12% and pD(2) = 6.51 +/- 0.20, 6.93 +/- 0.29 and 6.48 +/- 0.16, r espectively). Sodium nitroprusside (pD(2) = 6.76 +/- 0.29) and theophylline (pD(2) = 5.15 +/- 0.22) were effective inhibitors of myometrial contractio ns. Chromatographic separation of phosphodiesterase isoenzymes demonstrated that phosphodiesterase 4 is predominant but other phosphodiesterase isoenz ymes were also identified. In conclusion, phosphodiesterase 4 inhibitors al one or combined with beta(2)-adrenoceptor agonists have potential interest as tocolytic agents.