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  • Title: Effects and selectivity of CL 316243, beta-3-adrenoceptor agonist, in term-pregnant rat myometrium.
    Author: Kaya T, Karadas B, Altun A, Sarac İ, Bagcivan I.
    Journal: Gynecol Obstet Invest; 2012; 73(1):63-9. PubMed ID: 22189156.
    Abstract:
    BACKGROUND/AIMS: Recent evidence supports a predominant role of β(3)-adrenoceptors at the end of pregnancy in myometrium. This study was designed to characterize the pharmacology of the selective β(3)-adrenoceptor agonist CL 316243 on oxytocin-induced myometrial contractions and the levels of cAMP and cGMP of myometrial strips isolated from term-pregnant rats. METHODS: Myometrial strips were obtained from term-pregnant Wistar albino rats (n = 10), mounted in organ baths and tested for changes in isometric tension in response to CL 316243 (10(-10)-10(-5) M) on oxytocin-induced myometrial contractions. Effects of CL 316243 on cAMP and cGMP levels in isolated myometrial strips (n = 8) were evaluated by radioimmunoassay kits. We evaluated the effect of increasing concentrations of CL 316243 on myometrial contractions and on contractions of myometrial smooth muscle pretreated with metoprolol, ICI 118.551 and SR 59230A (β(1)-, β(2)-, β(3)-adrenoceptor antagonists, respectively, 10(-6) M). RESULTS: The inhibition of the amplitude of oxytocin-induced contractions by CL 316243 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). CL 316243 increased cAMP levels compared to the control group. CL 316243 increased cGMP levels, in the CL 316243 group more than in the control group, but this increase is less significant than cAMP levels. CONCLUSION: These results demonstrate that the inhibition of rat myometrial contractions with CL 316243 is mediated by β(3)-adrenoceptor subtype and increased cAMP and cGMP levels.
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