Add time:07/14/2019         Source:sciencedirect.com

Synthetic bovine parathyroid hormone containing the NH2 terminal 34 amino acids [bPTH-(1–34)] was recently demonstrated to inhibit oxytocin stimulated uterine contraction in vitro. The parathyroid hormone analogues [Nle8, Nle18, Tyr34]bPTH-(3–34)amide [NTA-(3–34)] and [Tyr34]bPTH-(7–34)amide [NTA-(7–34)] have been reported to act as inhibitors of antagonists of parathyroid hormone (PTH) in numerous assays. In the present study the effects of these PTH analogues on uterine contraction and the ability of these analogues to act as antagonists to the uterine inhibitory action of bPTH-(1–34) in vitro were investigated. The NTA-(3–34) fragment had no effect on oxytocin stimulated uterine contractions. However, the NTA-(3–34) fragment was able to alter the ability of bPTH(1–34) to reduce oxytocin stimulated uterine contraction in a dose-related manner. Bovine PTH(1–34) (0.3 μg/ml) reduced the contractile response obtained with oxytocin (0.5 mU/ml) by 20%. A dose of 15 μg/ml of NTA-(3–34) abolished this inhibitory action of bPTH-(1–34) on oxytocin stimulated uterine contraction. In contrast the NTA-(7–34) fragment itself, stimulated contraction of resting uterine horns in a dose-related manner; 3.0 μg/ml of NTA-(7–34) caused a change in gram tension of +1.5 grams. Bovine PTH-(1–34) was able to reduce the uterine contraction stimulated by NTA-(7–34) and 0.3 μg/ml of bPTH-(1–34) reduced the contractile response obtained with 3.0 μg/ml of NTA-(7–34) by as much as 70%. These results show that shortening of bPTH-(1–34) by two amino acids at the NH2 terminus results in loss of the previously defined uterine inhibitory action of the peptide. However, this fragment is capable of antagonizing the effect of bPTH-(1–34) in the uterine assay. The NTA-(7–34) fragment stimulated uterine contraction and thus had an action completely opposite that of bPTH-(1–34) inhibitory effect.

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