STRUCTURE-ACTIVITY STUDIES OF ANALOGS OF NEUROKININ-A MEDIATING CONTRACTION OF RAT UTERUS

A structure-activity study of compounds related to NKA was performed u sing uterus from the oestrogen-primed rat, a preparation thought to co ntain a significant population of NK2 receptors. The compounds tested included: NKA and its C-terminal fragments; NKA(4-10)-free acid; a ser ies of LAla monosubstituted analogues of NKA(4-10) and of NKA; [DAla(1 )]NKA; and a series of analogues of [Nle(10)]NKA(4-10) monosubstituted at position four, five or seven. Results suggest that the His at posi tion one of NKA is of little or no importance in contractile activity, while substitution or truncation of Lys at position two or substituti on of Thr at position three causes a decrease in potency. Results also confirm that amino acids at positions four, six, seven, nine and ten are very important for contractile activity of NKA and its analogues o n rat uterus. The similarity between the changes in potency obtained i n this study, and those obtained in rabbit pulmonary artery, an NK2 mo noreceptor preparation, provides further evidence for the presence of NK2 receptors in the uterus of the oestrogen-primed rat.