We wished to determine whether any evidence indicates that the ductus arteriosus has prostanoid receptors coupled to contractile pathways and whether the sensitivity of the ductus to the dilator effect of pros-taglandin E2 (PGE2) was inhibited by other prostanoids. Rings of ductus arteriosus were isolated from fetal New Zealand White rabbits (28 days of gestation) and mounted in vitro. In the presence of 1 [mu] M indomethacin, the vessel was relaxed with either 300 nM forskolin or 10 nAf PGE2, and cumulative concentration-contraction response curves to several synthetic prostanoids were obtained with or without a receptor antagonist when available. The vessel was also precontracted with 1 [mu] M indomethacin and 25 mM K+ in 13-14.5 kPa O2, and cumulative concentration-relaxation response curves to PGE2 were obtained with and without addition of prostanoids. In 300 nAf forskolin, both U46619 and sulprostone caused concentration-dependent contractions of the ductus in the nanomolar range (EC50 values, ie, the interpolated molar concentration of the drug causing 50% of its own eventual maximum response of 33 and 42 nM, respectively). Responses to GR63799X and PGF2 [alpha] were complicated by the fact that these agonists caused relaxation at high concentrations (>= 30 nM). The response to U46619 was shifted to the right by the thromboxane receptor antagonist EP 092. In 10 nM PGE2, U46619, sulprostone, and GR63799X elicited similar contractile responses, whereas PGF2 [alpha] had no effect. Incubation in 10 nM U46619 or PGF2 [alpha] had no effect on the sensitivity of the ductus to the dilator effect of PGE2, but 10 nM sulprostone increased the EC50 to PGE2 by 119% and 3 [mu] M sulprostone increased it by 157%. The fetal rabbit ductus arteriosus has contractile receptors for thromboxane and for PGE2. The contractile receptor for PGE2 appears to modulate the vessel's sensitivity to the dilator effect of PGE2.