Department of Urology, University of Munich, Munich, Germany.
Eur J Pharmacol. 2011 Jan 15;650(2-3):650-5. doi: 10.1016/j.ejphar.2010.10.052. Epub 2010 Oct 31.
Thromboxane A(2) (TXA(2)) induces contraction in different smooth muscle types via its receptor (TXA(2) receptor). However, any motoric role of TXA(2) in prostate smooth muscle tone has not been studied to date. Here, we investigated whether TXA(2) induces contraction of human prostate tissue. After ethical approval, prostate tissue was obtained from 47 patients undergoing radical prostatectomy. Effects of the TXA(2) analogue 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 TXA(2) synthase and TXA(2) receptors were examined by Western blot analysis and immunohistochemistry. Endogenous TXA(2) was quantified by enzyme immunoassay. U46619 induced concentration-dependent contractions of human prostate strips, with a maximum contraction at 3 μM. U46619-induced prostate contraction was significantly inhibited by Y27632 (30 μM) and by W7 (100 μM). TXA(2) synthase and TXA(2) receptors were detected by Western blot analysis. Immunohistochemical stainings showed that expression of TXA(2) synthase in prostate tissue was located to glandular cells, while prostate TXA(2) receptors were located to smooth muscle and glandular cells. The stable TXA(2) metabolite TXB(2) was detected by enzyme immunoassay in the prostate. TXA(2) induces contraction of isolated human prostate tissue by TXA(2) receptor activation. Prostate smooth muscle TXA(2) receptors are coupled to Rho kinase and Ca(2+)-dependent mechanisms. The distribution of TXA(2) synthase and TXA(2) receptors in the human prostate suggests TXA(2)-mediated paracrine epithelial-stromal interactions.
血栓素 A（2）（TXA（2））通过其受体（TXA（2）受体）诱导不同平滑肌类型的收缩。然而，迄今为止，尚未研究 TXA（2）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 TXA（2）是否诱导人前列腺组织收缩。在获得伦理批准后，从 47 名接受根治性前列腺切除术的患者中获得前列腺组织。在器官浴实验中研究了 TXA（2）类似物 U46619（（5Z）-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-羟基-1-辛烯基]-2-氧杂双环[2.2.1]庚-5-基]-5-庚酸）对分离的人前列腺条带的作用，实验中有无 Rho 激酶抑制剂 Y27632（trans-4-[(1R)-1-氨基乙基]-N-4-吡啶基环己烷甲酰胺二盐酸盐）或钙调蛋白拮抗剂 W7（N-（6-氨基己基）-5-氯-1-萘磺酰胺盐酸盐）。通过 Western blot 分析和免疫组织化学检查 TXA（2）合酶和 TXA（2）受体的表达。通过酶免疫测定定量测定内源性 TXA（2）。U46619 诱导人前列腺条带浓度依赖性收缩，在 3 μM 时达到最大收缩。U46619 诱导的前列腺收缩被 Y27632（30 μM）和 W7（100 μM）显著抑制。通过 Western blot 分析检测到 TXA（2）合酶和 TXA（2）受体。免疫组织化学染色显示前列腺组织中 TXA（2）合酶的表达定位于腺细胞，而前列腺 TXA（2）受体定位于平滑肌和腺细胞。通过酶免疫测定法在前列腺中检测到稳定的 TXA（2）代谢物 TXB（2）。TXA（2）通过 TXA（2）受体激活诱导分离的人前列腺组织收缩。前列腺平滑肌 TXA（2）受体与 Rho 激酶和 Ca（2+）依赖性机制偶联。TXA（2）合酶和 TXA（2）受体在人前列腺中的分布表明 TXA（2）介导的旁分泌上皮-间质相互作用。
