Oxytocic effect of trypsin on the isolated rat uterus

To study the oxytocic effect of trypsin, we measured the force of isometric contraction in uteri isolated from estrogenized rats exposed to trypsin (8.8 x 10(-10) to 1.7 x 10(-6) mol/L) either alone or in the presence of receptor antagonists to angiotensin II [saralasin ([Sar1,Ala8]angiotensin II) or DuP 753 (losartan)] or to kinins (D-[Arg0,Hyp3,Thi5,8,D-Phe7]-bradykinin). We found that saralasin or DuP 753, but not the kinin antagonist, displaced the dose-response curve to the right. Exposure to exogenous angiotensin I desensitized the preparation to further doses of either angiotensin I or II or trypsin, without altering the effects of oxytocin or bradykinin. Enalaprilat (an angiotensin I converting enzyme inhibitor) or pepstatin A (a renin inhibitor) also displaced the dose-response curve to trypsin to the right, without altering the effects of oxytocin or angiotensin II. Our results indicate that the response to trypsin is mediated by an agent produced from a substrate present in the uterus and acting on the angiotensin II type 1 receptor and are consistent with both renin and angiotensin I converting enzyme being involved in its mechanism of action, thus supporting the notions that the renin-angiotensin system may be important in the late stages of pregnancy and that serine proteases existing in the uterus may contribute to its activation.