Urologische Klinik & Poliklinik, Marchioninistr. 15, 81377 München.
Am J Physiol Renal Physiol. 2013 Nov 15;305(10):F1383-90. doi: 10.1152/ajprenal.00380.2013. Epub 2013 Sep 18.
Inhibition of prostate smooth muscle contraction is an important strategy for medical treatment of lower urinary tract symptoms (LUTS). Besides α1-adrenoceptors, prostate smooth muscle contraction is induced by activation of thromboxane (TXA2) receptors (TXA2-R). Here, we examined the effects of the TXA2-R antagonist picotamide on contraction of human prostate tissue. Prostate tissues were obtained from radical prostatectomy. The effects of picotamide (300 μM), L-665,240 (3 μM), and seratrodast (3 μM) on U46619-, electric field stimulation- (EFS-), phenylephrine-, and norepinephrine-induced contractions were studied in organ baths. Expression of TXA2-R and TXA2 synthase (TXS) was examined by fluorescence stainings. Picotamide, seratrodast, and L-655,240 inhibited concentration-dependent contractions induced by the TXA2 analog U46619. Picotamide, but not seratrodast or L-655,240, inhibited frequency-dependent contractions induced by EFS. Picotamide inhibited concentration-dependent contractions induced by norepinephrine or by the selective α1-adrenoceptor agonist phenylephrine. In prostate strips, where only submaximal contraction by a low dose of phenylephrine was induced, application of U46619 raised tone to maximum phenylephrine-induced tension. Immunoreactivity for TXA2-R and TXS was observed in the stroma and in epithelial cells of glands. Colocalization of both immunoreactivites was observed with the smooth muscle markers calponin and α-smooth muscle actin, with the epithelial marker pan-cytokeratin, and with prostate-specific antigen in the stroma and glands. The receptor antagonist picotamide inhibits α1-adrenergic, TXA2-mediated, and EFS-induced contractions in the human prostate. To the best of our knowledge, this is the first antagonist able to inhibit two different contraction systems in the prostate.
抑制前列腺平滑肌收缩是治疗下尿路症状（LUTS）的重要策略。除了α1-肾上腺素受体外，前列腺平滑肌的收缩还可通过血栓素（TXA2）受体（TXA2-R）的激活来诱导。在这里，我们研究了 TXA2-R 拮抗剂 picotamide 对人前列腺组织收缩的影响。前列腺组织取自根治性前列腺切除术。在器官浴中研究了 picotamide（300μM）、L-665,240（3μM）和 seratrodast（3μM）对 U46619、电场刺激（EFS）、苯肾上腺素和去甲肾上腺素诱导收缩的影响。通过荧光染色检查 TXA2-R 和 TXA2 合酶（TXS）的表达。Picotamide、seratrodast 和 L-655,240 抑制了 TXA2 类似物 U46619 诱导的浓度依赖性收缩。Picotamide 抑制了 EFS 诱导的频率依赖性收缩，但不抑制 seratrodast 或 L-655,240。Picotamide 抑制了去甲肾上腺素或选择性α1-肾上腺素受体激动剂苯肾上腺素诱导的浓度依赖性收缩。在前列腺条带中，仅用低剂量苯肾上腺素诱导出亚最大收缩，应用 U46619 将张力提高到最大苯肾上腺素诱导的张力。在基质和腺上皮细胞中观察到 TXA2-R 和 TXS 的免疫反应性。这两种免疫反应性与平滑肌标志物 calponin 和 α-平滑肌肌动蛋白、上皮标志物 pan-cytokeratin 以及基质和腺中的前列腺特异性抗原共定位。受体拮抗剂 picotamide 抑制了人前列腺中的 α1-肾上腺素能、TXA2 介导和 EFS 诱导的收缩。据我们所知，这是第一种能够抑制前列腺中两种不同收缩系统的拮抗剂。
