Thromboxane A2 induces contraction of human prostate smooth muscle by Rho kinase- and calmodulin-dependent mechanisms.
Thromboxane A2 induces contraction of human prostate smooth muscle by Rho kinase- and calmodulin-dependent mechanisms.
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Thromboxane A2 通过 Rho 激酶和钙调蛋白依赖性机制诱导人前列腺平滑肌收缩。
DOI：
10.1016/j.ejphar.2010.10.052
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发表时间：
2010
影响因子：
5
通讯作者：
M. Hennenberg
中科院分区：
文献类型：
--
作者：
F. Strittmatter;C. Gratzke;P. Weinhold;C. Steib;Anna C Hartmann;B. Schlenker;K. Andersson;P. Hedlund;C. Stief;M. Hennenberg
血栓素A2(TXA2)通过其受体(TXA2受体)诱导不同类型的血管收缩。然而，到目前为止，还没有人研究TXA2在前列腺平滑肌张力中的任何运动作用。在这里，我们研究了TXA2是否引起人前列腺组织的收缩。经伦理批准后，从47名接受根治性前列腺切除术的患者身上获得了前列腺组织。在器官浴实验中，研究了TXA2类似物(U46619((5Z)-7-[(1R，4S，5S，6R)-6-[(1E，3S)-3-hydroxy-1-octenyl]-2-oxabicyclo[2.2.1]hept-5-yl]-5-heptonic酸)在器官浴实验中的作用，包括Rho激酶抑制剂Y27632(trans-4-[(1R)-1-aminoethyl]-N-4-pyridinylcyclohexanecarboxamide二盐酸盐或钙调蛋白拮抗剂W7(N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamide盐酸盐。用Western印迹分析和免疫组织化学方法检测血栓素A2合成酶及其受体的表达。内源性TXA2用酶免疫法测定。U46619引起的人前列腺条收缩呈浓度依赖性，最大收缩时间为3μM。Y27632(30μM)和W7(100μM)对U46619引起的前列腺收缩有明显的抑制作用。Western印迹法检测血栓素A2合成酶及其受体的表达。免疫组织化学染色显示，TXA2合成酶在前列腺组织中的表达定位于腺体细胞，而前列腺癌组织中的TXA2受体定位于平滑肌和腺体细胞。用酶免疫法检测前列腺组织中稳定的TXA2代谢产物TXB2。TXA2通过激活TXA2受体诱导人前列腺组织收缩。前列腺肌TXA2受体与Rho激酶和钙依赖机制相偶联。TXA2合成酶和TXA2受体在人前列腺中的分布提示TXA2介导的旁分泌上皮-间质相互作用。
Thromboxane A2(TXA2) induces contraction in different smooth muscle types via its receptor (TXA2receptor). However, any motoric role of TXA2in prostate smooth muscle tone has not been studied to date. Here, we investigated whether TXA2induces contraction of human prostate tissue. After ethical approval, prostate tissue was obtained from 47 patients undergoing radical prostatectomy. Effects of the TXA2analogue U46619 ((5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxy-1-octenyl]-2-oxabicyclo[2.2.1]hept-5-yl]-5-heptonic acid) in isolated human prostate strips were studied in organ bath experiments with or without the Rho kinase inhibitor, Y27632 (trans-4-[(1R)-1-aminoethyl]-N-4-pyridinylcyclohexanecarboxamide dihydrochloride), or the calmodulin antagonist W7 (N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamide hydrochloride). Expression of TXA2synthase and TXA2receptors were examined by Western blot analysis and immunohistochemistry. Endogenous TXA2was quantified by enzyme immunoassay. U46619 induced concentration-dependent contractions of human prostate strips, with a maximum contraction at 3μM. U46619-induced prostate contraction was significantly inhibited by Y27632 (30μM) and by W7 (100μM). TXA2synthase and TXA2receptors were detected by Western blot analysis. Immunohistochemical stainings showed that expression of TXA2synthase in prostate tissue was located to glandular cells, while prostate TXA2receptors were located to smooth muscle and glandular cells. The stable TXA2metabolite TXB2was detected by enzyme immunoassay in the prostate. TXA2induces contraction of isolated human prostate tissue by TXA2receptor activation. Prostate smooth muscle TXA2receptors are coupled to Rho kinase and Ca2+-dependent mechanisms. The distribution of TXA2synthase and TXA2receptors in the human prostate suggests TXA2-mediated paracrine epithelial–stromal interactions.
影响因子：
--
作者：
MATSUDA, K;RUFF, A;HALUSHKA, PV
通讯作者：
HALUSHKA, PV
影响因子：
11.2
作者：
Nie, Daotai;Guo, Yande;Honn, Kenneth V.
通讯作者：
Honn, Kenneth V.