The STK16 inhibitor STK16-IN-1 inhibits non-adrenergic and non-neurogenic smooth muscle contractions in the human prostate and the human male detrusor
The STK16 inhibitor STK16-IN-1 inhibits non-adrenergic and non-neurogenic smooth muscle contractions in the human prostate and the human male detrusor
复制标题
DOI：
10.1007/s00210-019-01797-x
复制
发表时间：
2020-05-01
影响因子：
3.6
通讯作者：
Hennenberg, Martin
中科院分区：
文献类型：
--
作者：
Li, Bingsheng;Wang, Xiaolong;Hennenberg, Martin
混合性下尿路症状（LUTS）（提示良性前列腺增生的排尿症状加上可能由膀胱过度活动症引起的储尿症状）在男性中很常见。前列腺和/或膀胱平滑肌的不必要收缩已被暗示在男性LUTS的病理生理学。在这里，我们研究了丝氨酸/苏氨酸激酶16（STK 16）抑制剂STK 16-IN-1对前列腺和男性逼尿肌的人体组织收缩的影响。组织取自根治性膀胱切除术和根治性膀胱切除术。在器官浴中研究收缩，并通过Western印迹分析和荧光染色研究STK 16的表达。在前列腺组织中，STK 16-IN-1（1 μ M）抑制内皮素-1和血栓素A（2）类似物U46619诱导的收缩。STK 16-IN-1不改变去甲肾上腺素、α（1）-激动剂苯肾上腺素和甲氧胺或电场刺激（EFS）诱导的前列腺组织收缩。在男性逼尿肌组织中，STK 16-IN-1抑制由胆碱能激动剂卡巴胆碱和甲甲胆碱诱导的收缩，以及由U46619诱导的收缩。STK 16-IN-1不改变EFS诱导的逼尿肌组织收缩。前列腺和逼尿肌组织的蛋白质印迹分析显示与STK 16的分子量匹配的条带。使用STK 16抗体的前列腺组织的荧光染色导致平滑肌细胞中的免疫反应性。STK 16-IN-1选择性抑制男性前列腺中的非肾上腺素能/非神经源性平滑肌收缩，并在膀胱中达到有限程度。由于男性LUTS中的非肾上腺素能收缩可能是α（1）受体阻滞剂疗效有限和α（1）受体阻滞剂耐药症状的原因，因此评估混合LUTS中STK 16-IN-1与α（1）受体阻滞剂联合治疗的研究似乎是可行的。
Mixed lower urinary tract symptoms (LUTS) (voiding symptoms suggestive of benign prostatic hyperplasia plus storage symptoms, which can be caused by overactive bladder) are common in men. Unwanted contraction of prostate and/or bladder smooth muscle has been implied in the pathophysiology of male LUTS. Here, we examined effects of the serine/threonine kinase 16 (STK16) inhibitor STK16-IN-1 on contraction of human tissues from the prostate and male detrusor. Tissues were obtained from radical prostatectomy and radical cystectomy. Contractions were studied in an organ bath and STK16 expressions by Western blot analyses and fluorescence staining. In prostate tissues, STK16-IN-1 (1 mu M) inhibited contractions induced by endothelin-1 and the thromboxane A(2) analog U46619. Contractions of prostate tissues induced by noradrenaline, the alpha(1)-agonists phenylephrine and methoxamine, or electric field stimulation (EFS) were not changed by STK16-IN-1. In male detrusor tissues, STK16-IN-1 inhibited contractions induced by the cholinergic agonists carbachol and metacholine, and contractions induced by U46619. EFS-induced contractions of detrusor tissues were not changed by STK16-IN-1. Western blot analyses of prostate and detrusor tissues revealed bands matching the molecular weight of STK16. Fluorescence staining of prostate tissues using STK16 antibodies resulted in immunoreactivity in smooth muscle cells. STK16-IN-1 selectively inhibits non-adrenergic/non-neurogenic smooth muscle contractions in the male prostate and to limited extent in the bladder. Because non-adrenergic contractions in the male LUTS may account for limited efficacy of alpha(1)-blockers and for alpha(1)-blocker-resistant symptoms, studies assessing add-on of STK16-IN-1 to alpha(1)-blockers in mixed LUTS appear feasible.