The effects in the rat of two fragments of parathyroid hormone-related protein on uterine contractions in situ.

Synthetic parathyroid hormone fragment PTH(1-34) has been reported recently to inhibit uterine contractions stimulated by a variety of agonists. We have studied the effect in this system of the parathyroid hormone-related protein fragment PTHrP(1-34) which shows 60% homology with PTH over the first thirteen amino acid residues. The effects of two different PTHrP fragments on acetylcholine-stimulated uterine contractions in vitro were studied. Whereas synthetic hPTHrP(75-86 amide) (10(-9)-10(-7) M) was without effect, synthetic hPTHrP(1-34) (10(-9)-10(-7) M) was capable of inhibiting, in a dose-related fashion, uterine muscle contractions precontracted with 10(-6) M-acetylcholine. In a second series of experiments the bovine PTH(3-34) fragment itself was shown to have no stimulatory effect on acetylcholine-stimulated contractions. Also this fragment in an equimolar concentration (10(-7) M) failed to antagonize the effects of PTHrP(1-34) on acetylcholine-stimulated uterine contractions. However, a 100-fold excess molar concentration of bPTH(3-34) (10(-6) M) completely abolished the inhibitory action of hPTHrP(1-34) (10(-8) M) on acetylcholine-stimulated uterine contractions. These results clearly show that the inhibitory action of PTH(1-34) and PTHrP(1-34) on uterine contractions depends on the integrity of the amino-terminal region of the molecule.