The urinary tract is highly innervated by autonomic nerves which are essential in urinary tract development, the production of growth factors, and the control of homeostasis. These neural signals may become dysregulated in several genitourinary (GU) disease states, both benign and malignant. Accordingly, the autonomic nervous system is a therapeutic target for several genitourinary pathologies including cancer, voiding dysfunction, and obstructing nephrolithiasis. Adrenergic receptors (adrenoceptors) are G-Protein coupled-receptors that are distributed throughout the body. The major function of α1-adrenoceptors is signaling smooth muscle contractions through GPCR and intracellular calcium influx. Pharmacologic intervention of α-and β-adrenoceptors is routinely and successfully implemented in the treatment of benign urologic illnesses, through the use of α-adrenoceptor antagonists. Furthermore, cell-based evidence recently established the antitumor effect of α1-adrenoceptor antagonists in prostate, bladder and renal tumors by reducing neovascularity and impairing growth within the tumor microenvironment via regulation of the phenotypic epithelial-mesenchymal transition (EMT). There has been a significant focus on repurposing the routinely used, Food and Drug Administration-approved α1-adrenoceptor antagonists to inhibit GU tumor growth and angiogenesis in patients with advanced prostate, bladder, and renal cancer. In this review we discuss the current evidence on (a) the signaling events of the autonomic nervous system mediated by its cognate α- and β-adrenoceptors in regulating the phenotypic landscape (EMT) of genitourinary organs; and (b) the therapeutic significance of targeting this signaling pathway in benign and malignant urologic disease.

中文翻译：

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α-和 β-肾上腺素能信号在表型靶向中的作用：在良性和恶性泌尿系统疾病中的意义


泌尿道受到自主神经的高度支配，自主神经对于泌尿道发育、生长因子的产生和体内平衡的控制至关重要。这些神经信号可能在多种泌尿生殖 (GU) 疾病状态（良性和恶性）中失调。因此，自主神经系统是多种泌尿生殖病理的治疗靶点，包括癌症、排尿功能障碍和梗阻性肾结石。肾上腺素能受体（肾上腺素受体）是分布于全身的 G 蛋白偶联受体。 α1-肾上腺素受体的主要功能是通过 GPCR 和细胞内钙流入向平滑肌收缩发出信号。通过使用α-肾上腺素受体拮抗剂，α-和β-肾上腺素受体的药物干预已常规成功地用于治疗良性泌尿系统疾病。此外，最近基于细胞的证据证实，α1-肾上腺素受体拮抗剂通过调节表型上皮间质转化 (EMT) 减少新生血管并损害肿瘤微环境内的生长，从而在前列腺、膀胱和肾肿瘤中发挥抗肿瘤作用。人们非常关注重新利用常规使用的、美国食品和药物管理局批准的 α1-肾上腺素受体拮抗剂来抑制晚期前列腺癌、膀胱癌和肾癌患者的 GU 肿瘤生长和血管生成。在这篇综述中，我们讨论了以下方面的当前证据：(a) 由同源 α- 和 β- 肾上腺素受体介导的自主神经系统信号事件，调节泌尿生殖器官的表型景观 (EMT)； (b)针对良性和恶性泌尿系统疾病的该信号通路的治疗意义。