Comparison of effects of formoterol and BRL 37344 on isolated term-pregnant rat myometrial strips in vitro

Abstract

This study was designed to compare the effects of beta-adrenoccptoy agonists formoterol and BRL 37344 on spontaneous contractions and the levels of cAMP and cGMP of myometrial strips isolated from timed-pregnant rats. Myometrial strips were obtained from term-pregnant Wistar albino rats (n = 12), mounted in organ baths and tested for changes in isometric tension in response to formoterol and BRL 37344. We evaluated the effect of increasing concentrations of formoterol and BRL 37344 on oxytocin-induced myometrial contractions and on contractions of myometrial smooth muscle pretreated with metoprolol, ICI 118.551 and SR 59230A (beta(1), beta(2), beta(3)-adrenoceptor antagonist, respectively, 10-6 M). Effects of formoterol and BRL 37344 on cAMP and cGMP levels in isolated myornetrial strips (n=6) were evaluated by radio immunoassay kits. Formoterol (10(-12) - 10(-8) M) and BRL 37344 (10(-11)-10(-5) M) concentration-dependently decreased the amplitude of oxytocin-induced contractions. E-max value (100%) of formoterol was increased significantly more than E-max value (70.6%) of BRL 37344 (P < 0.05), with no change in pD(2) value (9.54 +/- 0.12 and 9.12 +/- 0.12, respectively). The inhibition of the amplitude of oxytocin-induced contractions by formoterol was antagonized with ICI 118.551 (10(-6) M), but they were not changed by nictoprolol (10(-6) M) or SR 59230A (10(-6) M). The inhibition of the amplitude of oxytocin-induced contractions by BRL 37344 were antagonized with SR 59230A (10(-6) M), but they were not changed by metoprolol (10(-6) M) or ICT 118.551 (10(-6) M). Formoterol and BRL 37344 increased cAMP levels. BRL 37344 increased cGMP levels in BRL 37344 group more than control group, but this increase is less significant than cAMP levels (P > 0.05). Fon-noterol and BRL 37344 decreased amplitude of myometrial contractions with similar potency, but efficacy of forinoterol was better than BRL 37344. (c) 2005 Elsevier B.V. All rights reserved.