New strategies for inhibition of non-adrenergic prostate smooth muscle contraction by pharmacologic intervention

The Prostate
Qingfeng YuMartin Hennenberg

Abstract

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. Prostate tissues were obtained from radical prostatectomy. Contractions were studied in an organ bath. Viability of cultured stromal cells was assessed by C...Continue Reading

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Citations

Jun 25, 2020·British Journal of Pharmacology·Bingsheng LiMartin Hennenberg
Apr 24, 2020·Frontiers in Cell and Developmental Biology·Maria Del Mar MaldonadoSuranganie Dharmawardhane
Jun 4, 2021·Frontiers in Oncology·Jiaxin LiangQianjin Liao

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