Research Article| Volume 13, ISSUE 2, P119-128, February 1984

Effect of ritodrine hydrochloride and dibutyryl cyclic AMP on contractile activity and prostanoid production of uteri from pregnant rats in vitro

  • Norman H. Dubin
    reprint requests to ND
    Department of Gynecology and Obstetrics, The Johns Hopkins University School of Medicine, Park Building, Rm. B202, 601 N. Broadway, Baltimore, Maryland, 21205, USA
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  • Ramesh B. Ghodgaonkar
    Department of Gynecology and Obstetrics, The Johns Hopkins University School of Medicine, Park Building, Rm. B202, 601 N. Broadway, Baltimore, Maryland, 21205, USA
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      Ritodrine hydrochloride is a β-mimetic amine which is used to inhibit premature labor. While the mechanism of action of β-mimetic drugs is believed to be a function of its action on the adenylate cyclase system, the drug may also act via other mechanisms. We examined the effect of this drug on both contractile activity and prostanoid production using an Math Eq preparation of a uterus from a 21-day pregnant rat. Two uterine segments were simultaneously studied in separate incubation chambers.Ritodrine (2.0 mg/ml) was added to one tissue chamber while the other tissue served as a control. Frequency and contractile force were monitored polygraphically for 45 min.Incubation medium was then removed for analysis of prostaglandin E2 (PGE2), PGF, 6-keto-PGF, and thromboxane B2 (TXB2) by radioimmunoassay. Ritodrine-treated uteri demonstrated a contractile force which was 16.8% of that of the control, a significant decrease. Ritodrine-treated uteri also produced less prostanoids. The greatest effect was on PGE production (27.3% of the control, p <0.001). The effect of ritodrine on the other prostanoids was less pronounced (PGF, 71%; 6-keto-PGF 84%; TXB2, 67% of the control). The presence of 0.2 mM dibutyryl cAMP in the incubation media also suppressed contractile force; however, prostanoids were not reduced and in some cases were elevated.It is concluded that one effect of ritodrine is a reduction in prostanoid production, predominately PGE2 and this in part may play a role in the drug's efficacy. The reduction does not appear to be mediated through the adenylate cyclase system.
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