Department of Urology, University Hospital Munich, LMU Munich, Munich, Germany.
Prostate. 2022 Jan;82(1):59-77. doi: 10.1002/pros.24248. Epub 2021 Oct 11.
Prostate smooth muscle contraction is promoted by receptor-induced activation of intracellular signaling pathways. The presumed involvement in etiology and medical treatment of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) imparts a high clinical relevance to prostate smooth muscle contraction, which is contrasted by incomplete understanding at the molecular level. Involvement of protein kinase C (PKC) has been commonly assumed, but available studies were limited to nonhuman prostate smooth muscle or cell cultures. Here, we examined the effects of the PKC inhibitors Go6983 and GF109203x on contractions of human prostate tissues.
Prostate tissues were obtained from radical prostatectomy. Contractions were induced by electric field stimulation (EFS), α -adrenergic agonists (noradrenaline, phenylephrine, methoxamine), thromboxane A analog U46619, endothelin-1, or calcium chloride in an organ bath.
GF109203X (500 nM) and Go6983 (300 nM) reduced EFS-, noradrenaline-, phenylephrine-, methoxamine-, and U46619-induced contractions of human prostate tissues, with maximum inhibitions approaching up to 55%. Using concentrations of 3 µM, GF109203X and Go6983 inhibited EFS- and noradrenaline-induced contractions, with similar effect sizes as 500 and 300 nM, respectively. Endothelin-1-induced contractions were not inhibited by GF109203X, and to neglectable extent by Go6983. After depolarization in calcium-free solution, calcium chloride-induced concentration-dependent contractions, which were inhibited by GF109203X and Go6983.
GF109203X and Go6983 inhibit neurogenic, α -adrenergic, and thromboxane A -induced smooth muscle contractions in the human prostate, suggesting a role of PKC for human prostate smooth muscle contraction. The inhibition may by be imparted by inhibition of calcium sensitivity.
前列腺平滑肌收缩是由受体诱导的细胞内信号通路激活促进的。 它被认为与下尿路症状（LUTS）的病因和治疗有关，这些症状提示良性前列腺增生（BPH），这赋予了前列腺平滑肌收缩高度的临床相关性，但在分子水平上的理解仍不完整。 蛋白激酶 C（PKC）的参与已被普遍假设，但现有研究仅限于非人类前列腺平滑肌或细胞培养物。 在这里，我们检查了 PKC 抑制剂 Go6983 和 GF109203x 对人前列腺组织收缩的影响。
从根治性前列腺切除术获得前列腺组织。 在器官浴中通过电场刺激（EFS），α-肾上腺素能激动剂（去甲肾上腺素，苯肾上腺素，甲氧胺），血栓烷 A 类似物 U46619，内皮素-1 或氯化钙诱导收缩。
GF109203X（500 nM）和 Go6983（300 nM）减少了 EFS，去甲肾上腺素，苯肾上腺素，甲氧胺和 U46619 诱导的人前列腺组织收缩，最大抑制率接近 55％。 使用 3 µM 的浓度，GF109203X 和 Go6983 抑制了 EFS 和去甲肾上腺素诱导的收缩，其作用大小与 500 和 300 nM 相似。 GF109203X 不抑制内皮素-1 诱导的收缩，而 Go6983 抑制作用可忽略不计。 在无钙溶液中去极化后，氯化钙诱导浓度依赖性收缩，GF109203X 和 Go6983 均可抑制该收缩。
GF109203X 和 Go6983 抑制人前列腺中的神经源性，α-肾上腺素能和血栓烷 A 诱导的平滑肌收缩，表明 PKC 参与人前列腺平滑肌收缩。 抑制作用可能是通过抑制钙敏感性赋予的。
