Kojima Yoshiyuki, Hayase Masa, Imura Makoto, Okada Shinsuke, Kubota Yasue, Sasaki Shoichi, Hayashi Yutaro, Kohri Kenjiro
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences.
Hinyokika Kiyo. 2008 Jun;54(6):457-62.
Alpha 1-adrenoceptors (alpha1-ARs) play a role in the regulation of prostatic smooth muscle tone, and are critical mediators of lower urinary tract symptoms (LUTS) and pathophysiology in benign prostatic hyperplasia (BPH). Three subtypes (alpha1a, alpha1b, alpha1d) have been identified by molecular cloning techniques. Although the reasons for the existence of three subtypes remain elusive, recent findings suggest a role of subtype and tissue-specific regulation. We examined the role of each alpha1-AR-subtype in the prostate to apply some new findings obtained from basic research for the clinical treatment. We have demonstrated that the mRNA expression levels of alpha1-AR-subtypes in the prostate differed among patients and that the genetic background differences of patients with BPH were responsible for the diverse responses to subtype-selective alpha1-blockers. In addition, both alpha1a- and alpha1d-AR-subtypes play a significant role in the spontaneous contraction of human prostate and, especially alpha1d-AR-subtypes may also control the cell growth of the prostate. Clarification of the mechanism of alpha1-AR subtypes in the prostate will provide more effective therapy for BPH patients.
α1肾上腺素能受体(α1-ARs)在前列腺平滑肌张力调节中发挥作用,并且是良性前列腺增生(BPH)患者下尿路症状(LUTS)及病理生理学的关键介质。通过分子克隆技术已鉴定出三种亚型(α1a、α1b、α1d)。尽管三种亚型存在的原因仍不明确,但最近的研究结果表明存在亚型及组织特异性调节作用。我们研究了每种α1-AR亚型在前列腺中的作用,以便将基础研究中获得的一些新发现应用于临床治疗。我们已经证明,前列腺中α1-AR亚型的mRNA表达水平在患者之间存在差异,并且BPH患者的遗传背景差异是对亚型选择性α1阻滞剂产生不同反应的原因。此外,α1a和α1d-AR亚型在人前列腺的自发收缩中均起重要作用,尤其是α1d-AR亚型可能还控制着前列腺的细胞生长。阐明前列腺中α1-AR亚型的机制将为BPH患者提供更有效的治疗方法。