Pennefather Jocelyn N, Patak Eva, Ziccone Sebastian, Lilley Alison, Pinto Francisco M, Page Nigel M, Story Margot E, Grover Sonia, Candenas M Luz
Department of Anaesthesia, Royal Women's Hospital, Carlton, Victoria 3053, Australia.
Biol Reprod. 2006 Sep;75(3):334-41. doi: 10.1095/biolreprod.106.051508. Epub 2006 May 17.
Regulation of the contractile effects of tachykinins and histamine on the human uterus was investigated with biopsy sections of the outer myometrial layer. The effects of neurokinin A (NKA) and human hemokinin-1 (hHK-1) in tissues from pregnant but not from nonpregnant women were enhanced by the inhibition of neprilysin. The effects of NKA and eledoisin were blocked by the NK2 receptor antagonist SR 48968 but not by the NK1 receptor antagonist SR 140333 in tissues from both groups of women. Human HK-1 acted as a partial agonist blocked by SR 48968 and, to a lesser extent, by SR 140333; endokinin D was inactive. In tissues from pregnant women, responses to high potassium-containing Krebs solution were 2-3-fold higher than those from nonpregnant women. Mepyramine-sensitive maximal responses to histamine were similarly enhanced. The absolute maximum responses to NKA and its stable NK2 receptor-selective analogue, [Lys5MeLeu9Nle10]NKA(4-10), were increased in pregnancy, but their efficacies relative to potassium responses were decreased. Tachykinin potencies were lower in tissues from pregnant women than in those from nonpregnant women. These data 1) show for the first time that hHK-1 is a uterine stimulant in the human, 2) confirm that the NK2 receptor is predominant in mediating tachykinin actions on the human myometrium, and 3) indicate that mammalian tachykinin effects are tightly regulated during pregnancy in a manner that would negate an inappropriate uterotonic effect. The potencies of these peptides in tissues from nonpregnant women undergoing hysterectomy are consistent with their possible role in menstrual and menopausal disorders.
利用子宫外肌层活检切片研究了速激肽和组胺对人子宫收缩作用的调节。在妊娠妇女而非未妊娠妇女的组织中，抑制中性内肽酶可增强神经激肽A（NKA）和人血红蛋白-1（hHK-1）的作用。在两组妇女的组织中，NKA和伊氏缩胆囊肽的作用均被NK2受体拮抗剂SR 48968阻断，但未被NK1受体拮抗剂SR 140333阻断。人HK-1起部分激动剂作用，可被SR 48968阻断，在较小程度上也可被SR 140333阻断；内激肽D无活性。在妊娠妇女的组织中，对含高钾的 Krebs 溶液的反应比未妊娠妇女的高2至3倍。对组胺的美吡拉敏敏感最大反应也同样增强。妊娠时对NKA及其稳定的NK2受体选择性类似物[Lys5MeLeu9Nle10]NKA(4 - 10)的绝对最大反应增加，但其相对于钾反应的效能降低。妊娠妇女组织中速激肽的效力低于未妊娠妇女组织中的效力。这些数据1）首次表明hHK-1是人体内的子宫刺激剂，2）证实NK2受体在介导速激肽对人子宫肌层的作用中占主导地位，3）表明哺乳动物速激肽的作用在妊娠期间受到严格调节，其方式可消除不适当的子宫收缩作用。这些肽在接受子宫切除术的未妊娠妇女组织中的效力与它们在月经和绝经紊乱中可能起的作用一致。
