Molecular Human Reproduction, Vol. 6, No. 6, 549-554,
June 2000
© 2000 European Society of Human Reproduction and Embryology
Pregnancy |
Activation of neurokinin NK2 receptors by tachykinin peptides causes contraction of uterus in pregnant women near term
1 Department of Pharmacology, Monash University, Clayton, Victoria, 3168 and 2 Department of Anaesthetics, Royal Women's Hospital, Carlton, Victoria, 3053, Australia
Abstract
The aim of this study was firstly to elucidate whether the mammalian tachykinins substance P (SP), neurokinin A (NKA) and neurokinin B (NKB)-regulated contractility of myometrium obtained from near-term pregnant women, and secondly to investigate the receptor subtype(s) responsible. In the presence of peptidase inhibitors, i.e. thiorphan (3 µmol/l; endopeptidase 24.11 inhibitor), captopril (10 µmol/l; angiotensin converting enzyme inhibitor) and bestatin (10 µmol/l; aminopeptidase inhibitor); all three mammalian tachykinins elicited concentration-related contractions of isolated myometrial preparations. The rank order of agonist potency of the mammalian tachykinins in the presence of the peptidase inhibitors was NKA > SP = NKB, indicating that the contractile effects were mediated by activation of an NK2 receptor. The NK2 receptor-selective agonist, [Lys5, MeLeu9, Nle10]NKA(4–10), produced concentration-related contractile responses, while the respective NK1 and NK3 receptor-selective agonists, [Sar9,Met(O2)11]SP and [N-MePhe7]NKB, had no effect either in the absence or presence of the peptidase inhibitors. The NK2 receptor-selective antagonist, SR48968, produced concentration-related rightward shift in the log concentration curve to [Lys5, MeLeu9, Nle10]NKA(4–10). This study shows that tachykinins elicit contractile effects on human myometrium obtained from pregnant women near term, and that these effects are mediated by an NK2 receptor. An excitatory effect of the tachykinins on these preparations could indicate a physiological role for these peptides in enhancing contractility of the uterus in women at term.
human uterus/NK2 receptors/peptidase inhibitors/pregnancy/tachykinins
Notes
3 To whom correspondence should be addressed at: Department of Pharmacology, Monash University, Clayton, Vic 3800, Australia. E-mail: margot.story{at}med.monash.edu.au
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