| Popis: |
Contractility studies were undertaken to determine the nature of the receptors mediating responses to tachykinins in uteri of oestrogen-treated mice. In the presence of thiorphan, (3 μM), captopril (10 μM) and bestatin (10 μM), substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) produced concentration-related contractions of uterine preparations. The order of potency was SP NKA>NKB. Neither atropine (0.1 μM) nor l-NOLA (100 μM), nor indomethacin (10 μM) alone or in combination with either ranitidine (10 μM) or mepyramine (10 μM), affected responses to SP. These findings indicate that SP actions are not mediated or modulated through the release of acetylcholine, nitric oxide, prostanoids or histamine. In the presence of peptidase inhibitors, the tachykinin NK1 receptor-selective agonist [Sar9Met(O2)11]SP, produced a concentration-dependent contractile effect. The tachykinin NK2 and NK3 receptor-selective agonists [Lys5MeLeu9Nle10]NKA(4-10) and [MePhe7]NKB were relatively inactive. The potencies of SP analogues in which Glu replaced Gln5 and/or Gln6 were similar to that of SP. The tachykinin NK1 receptor-selective antagonist, SR140333 (10 nM), alone or combined with the tachykinin NK2 receptor-selective antagonist, SR48968 (10 nM), shifted log concentration curves to SP, NKA and NKB to the right. SR140333 (10 nM) reduced the effect of [Sar9Met(O2)11]SP. SR48968 did not affect responses to SP or [Sar9Met(O2)11]SP, but reduced the effect of higher concentrations of NKA and shifted the log concentration-response curve to NKB to the right. The tachykinin NK3 receptor-selective antagonist, SR 142801 (0.3 μM), had little effect on responses to SP and NKB. We conclude that the tachykinin NK1 receptor mediates contractile effects of SP, NKA and NKB and [Sar9Met(O2)11]SP in myometrium from the oestrogen-primed mouse. The tachykinin NK2 receptor may also participate in the responses to NKA and NKB. British Journal of Pharmacology (2002) 137, 1247–1254. doi:10.1038/sj.bjp.0704996 |
