Plasma Oxytocinase: The Synthesis and Biological Properties of the First Prodoct of the Degradation of Oxytocin by this Enzyme

Abstract

Oxytocin is hydrolytically cleaved in the presence of plasma oxytocinase to give an acyclic peptide, tyrosyl-isoleucyl-glutaminyl-asparaginyl-S-(S-cysteine)-cysteinyl-prolyl-leucyl-glycinamide (1,2-acyclic oxytocin). The synthesis of this peptide is described. It is shown to be of very low potency in milk-ejection-like activity and uterotonic activity. It does not inhibit the expression of these activities by oxytocin, suggesting that it does not interfere with the hormone's binding to target tissues. The presence of 1,2-acyclic oxytocin slightly inhibits the rate of degradation of oxytocin by plasma from pregnant women, in contrast to the marked inhibition of the degradation of cystine di-β-naphthylamide. The K_m for the degradation of oxytocin is 30 times smaller than that of the degradation of cystine di-β-naphthylamide, which is of the same order as the K_i for the inhibition of the degradation of cystine di-β-naphthylamide by 1,2-acyclic oxytocin. These results, together with information on the substrate specificity of plasma oxytocinase with respect to the N-terminal amino acid residue, suggest that there are molecular features of oxytocin other than its N-terminal residue that facilitate its interaction with plasma oxytocinase.