Structure-activity studies of analogues of neurokinin A mediating contraction of rat uterus.
A structure-activity study of compounds related to NKA was performed using uterus from the oestrogen-primed rat, a preparation thought to contain a significant population of NK2 receptors. The compounds tested included: NKA and its C-terminal fragments; NKA(4-10)-free acid; a series of LAla monosubstituted analogues of NKA(4-10) and of NKA; [DAla1]NKA; and a series of analogues of [Nle10]NKA(4-10) monosubstituted at position four, five or seven. Results suggest that the His at position one of NKA is of little or no importance in contractile activity, while substitution or truncation of Lys at position two or substitution 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 on rat uterus. The similarity between the changes in potency obtained in this study, and those obtained in rabbit pulmonary artery, an NK2 monoreceptor preparation, provides further evidence for the presence of NK2 receptors in the uterus of the oestrogen-primed rat.
Fisher
L
L
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Pennefather
J N
JN
D000409:Alanine; D019943:Amino Acid Substitution; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D015288:Neurokinin A / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018041:Receptors, Neurokinin-2 / Q000502:physiology; D013329:Structure-Activity Relationship; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects* / Q000502:physiology
D010446:Peptide Fragments; D018041:Receptors, Neurokinin-2; D004958:Estradiol; C007630:estradiol 17 beta-cypionate; D015288:Neurokinin A; D000409:Alanine