The vasoactive potential of kisspeptin-10 in the peripheral vasculature.
The vasoactive potential of kisspeptin-10 in the peripheral vasculature.
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DOI：
10.1371/journal.pone.0014671
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发表时间：
2011-02-09
期刊：
影响因子：
3.7
通讯作者：
Brain SD
中科院分区：
文献类型：
--
作者：
Sawyer I;Smillie SJ;Bodkin JV;Fernandes E;O'Byrne KT;Brain SD
Kiss 1蛋白的剪接产物（kisspeptins）已被证明参与多种功能，包括青春期、转移和人类大动脉中的血管收缩。循环Kisspeptin-10（Kp-10）血浆水平在正常个体中较低，但在各种疾病状态以及妊娠期间升高。在这里，我们研究了Kp-10的潜力，最短的生物活性kisspeptin，影响微血管效应，集中在皮肤血管。在CD 1小鼠背部皮肤中，通过Evans蓝白蛋白染料外渗评估，KP-10导致水肿形成的剂量依赖性增加（0.3- 10 nmol/注射部位）。水肿形成被组胺H1受体拮抗剂美托咪胺抑制。反应特征为注射部位的苍白环，与血管收缩活性一致。因此，通过皮内注射99 m锝的清除率来评估背部皮肤血流的变化。发现Kp-10显著降低清除率，与血流减少一致，并为血管收缩活性提供了进一步的证据。与环氧合酶抑制剂吲哚美辛共同治疗可部分抑制清除率降低。最后，在正常和血管紧张素II诱导的高血压小鼠的心脏、主动脉和肾脏样本中观察到kisspeptin受体基因（Kiss 1 R）而非kisspeptin肽基因（Kiss 1）mRNA表达的证据，每个样本中观察到的mRNA水平相似。我们有证据表明kisspeptin-10具有两种外周血管活性作用。首先，血浆外渗指示诱导水肿形成的能力，其次减少外周血流量，指示微血管收缩。因此，Kp-10在外周微血管中具有血管活性。
Splice products of the Kiss1 protein (kisspeptins) have been shown to be involved in a diverse range of functions, including puberty, metastasis and vasoconstriction in large human arteries. Circulating Kisspeptin-10 (Kp-10) plasma levels are low in normal individuals but are elevated during various disease states as well as pregnancy. Here, we investigated the potential of Kp-10, the shortest biologically active kisspeptin, to influence microvascular effects, concentrating on the cutaneous vasculature. Kp-10 caused a dose-dependent increase in oedema formation (0.3–10nmol/injection site), assessed by Evans Blue albumin dye extravasation, in the dorsal skin of CD1 mice. Oedema formation was shown to be inhibited by the histamine H1 receptor antagonist mepyramine. The response was characterised by a ring of pallor at the injection site in keeping with vasoconstrictor activity. Therefore, changes in dorsal skin blood flow were assessed by clearance of intradermally injected 99mtechnetium. Kp-10 was found to significantly reduce clearance, in keeping with decreased blood flow and providing further evidence for vasoconstrictor activity. The decreased clearance was partially inhibited by co-treatment with the cyclo-oxygenase inhibitor indomethacin. Finally evidence for the kisspeptin receptor gene (Kiss1R), but not the kisspeptin peptide gene (Kiss1), mRNA expression was observed in heart, aorta and kidney samples from normal and angiotensin II induced hypertensive mice, with similar mRNA levels observed in each. We have evidence for two peripheral vasoactive roles for kisspeptin-10. Firstly, plasma extravasation indicative of ability to induce oedema formation and secondly decreased peripheral blood flow, indicating microvascular constriction. Thus Kp-10 has vasoactive properties in the peripheral microvasculature.
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DOI：
10.1152/ajpendo.00426.2009
发表时间：
2010-02
期刊：
American journal of physiology. Endocrinology and metabolism
影响因子：
--
作者：
Curtis AE;Cooke JH;Baxter JE;Parkinson JR;Bataveljic A;Ghatei MA;Bloom SR;Murphy KG
通讯作者：
Murphy KG
DOI：
10.1073/pnas.1834399100
发表时间：
2003-09-16
影响因子：
11.1
作者：
de Roux, N;Genin, E;Milgrom, E
通讯作者：
Milgrom, E
影响因子：
8.2
作者：
Hauge-Evans, A. C.;Richardson, C. C.;Jones, P. M.
通讯作者：
Jones, P. M.
影响因子：
4.8
作者：
Muir, AI;Chamberlain, L;Harrison, DC
通讯作者：
Harrison, DC
影响因子：
10.3
作者：
Lee, JH;Miele, ME;Welch, DR
通讯作者：
Welch, DR