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

Ritodrine hydrochloride is a beta-mimetic amine which is used to inhibit premature labor. While the mechanism of action of beta-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 in vitro 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), PGF2 alpha, 6-keto-PGF1 alpha, 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 less than 0.001). The effect of ritodrine on the other prostanoids was less pronounced (PGF2 alpha, 71%; 6-keto-PGF1 alpha, 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, predominantly 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.