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

Jan 4, 2006European journal of pharmacology

Comparing the effects of two drugs on muscle strips from pregnant rat wombs in the lab

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Abstract

Formoterol significantly increased the maximum effect (E(max)) value to 100%, compared to 70.6% for BRL 37344 (P<0.05).

Formoterol and BRL 37344 concentration-dependently decreased the amplitude of oxytocin-induced contractions in isolated myometrial strips.
The inhibition of contractions by formoterol was reversed by the beta2-adrenoceptor antagonist ICI 118.551, while BRL 37344's effect was reversed by the beta3-adrenoceptor antagonist SR 59230A.
Both drugs elevated cAMP levels in myometrial strips, with BRL 37344 also increasing cGMP levels, though this increase was less pronounced.
The efficacy of formoterol in reducing contraction amplitude was greater than that of BRL 37344, despite both having similar potency.

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This study was designed to compare the effects of beta-adrenoceptor 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 (beta1, beta2, beta3-adrenoceptor antagonist, respectively, 10(-6) M). Effects of formoterol and BRL 37344 on cAMP and cGMP levels in isolated myometrial strips (n=6) were evaluated by radioimmunoassay 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 metoprolol (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 ICI 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). Formoterol and BRL 37344 decreased amplitude of myometrial contractions with similar potency, but efficacy of formoterol was better than BRL 37344.

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

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