Fig. 1.

Uroguanylin relaxes oxytocin-stimulated contractions in a dose-dependent, pGC-C-mediated fashion in pregnant guinea pig myometrium. A, in the pregnant guinea myometrium (50–60 days gestation) 10 nM uGN relaxes the tissue with a reproducible effect on peak height and frequency of contraction. B, no such effect is seen in tissues from estrogen-primed nonpregnant animals even at 100 nM. Traces are representative examples. Effects were reproducible after washout and were seen both early and late in the recording. C, contractile tension was measured in grams from area under the curve (AUC) for 15 min of oxytocin-stimulated contractile activity in replicate pregnant guinea pig tissues (n = 6) in the presence or absence of 2Cl-ATP, ODQ, or isatin. The uGN relaxation was dose-dependent and significant at 3 nM uGN. Uroguanylin stimulation in the presence of 2Cl-ATP (1 μM) or isatin (10 μM) prevented the relaxation to 100 nM uGN. ODQ (10 μM) had no significant effect on the uGN-mediated relaxation. Data are mean ± S.E.M. from two replicate tissues from each of six animals (50–60 days gestation). **, p < 0.01; ***, p < 0.001.