New strategies for inhibition of non‐adrenergic prostate smooth muscle contraction by pharmacologic intervention
New strategies for inhibition of non‐adrenergic prostate smooth muscle contraction by pharmacologic intervention
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DOI：
10.1002/pros.23780
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发表时间：
2019-05
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通讯作者：
Qingfeng Yu;C. Gratzke;Yiming Wang;Xiaolong Wang;Bingsheng Li;F. Strittmatter;A. Herlemann;Ruixiao Wang;A. Tamalunas;R. Waidelich;C. Stief;M. Hennenberg
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文献类型：
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作者：
Qingfeng Yu;C. Gratzke;Yiming Wang;Xiaolong Wang;Bingsheng Li;F. Strittmatter;A. Herlemann;Ruixiao Wang;A. Tamalunas;R. Waidelich;C. Stief;M. Hennenberg
α1‐肾上腺素受体拮抗剂（α1‐阻滞剂）抑制前列腺平滑肌收缩是良性前列腺增生下尿路症状的一线药物治疗。增生前列腺平滑肌张力增高可引起尿道梗阻，引起膀胱出口梗阻和排尿症状。然而，α1‐阻滞剂的疗效有限，因为非肾上腺素能介质包括内皮素‐1和血栓素A2 （TXA2）与α1‐肾上腺素受体平行增加前列腺平滑肌张力。尽管使用α1‐阻滞剂治疗，这可能维持尿道梗阻。因此，未来更有效的治疗方案需要同时针对α1 -肾上腺素能和非肾上腺素能收缩。最近，一些化合物被报道能抑制肾上腺素能性或神经源性前列腺收缩，然而，它们对非肾上腺素能性收缩的作用尚不清楚。在这里，我们研究了Rac - GTPase、Src家族激酶（SFKs）和p21活化激酶（PAKs）抑制剂对非肾上腺素能性前列腺收缩的影响。
Inhibition of prostate smooth muscle contraction by α1‐adrenoceptor antagonists (α1‐blockers) is a first‐line medical treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Increased smooth muscle tone in the hyperplastic prostate may drive urethral obstruction, resulting in bladder outlet obstruction and voiding symptoms. However, efficacy of α1‐blockers is limited, as non‐adrenergic mediators including endothelin‐1 and thromboxane A2 (TXA2) increase prostate smooth muscle tension in parallel to α1‐adrenoceptors. This may maintain urethral obstruction despite therapy with α1‐blockers. Consequently, future treatment options with higher efficacy need to target α1‐adrenergic and non‐adrenergic contractions simultaneouly. Recently, several compounds were reported to inhibit adrenergic or neurogenic prostate contractions, however, their effects on non‐adrenergic contraction are unknown. Here, we examined effects of inhibitors for Rac‐GTPase, Src family kinases (SFKs), and p21‐activated kinases (PAKs) on non‐adrenergic prostate contractions.