The influences of 5alpha-reductase inhibitor dutasteride on contraction and alpha1-adrenoceptor expression in rat prostate
The influences of 5alpha-reductase inhibitor dutasteride on contraction and alpha1-adrenoceptor expression in rat prostate
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5α还原酶抑制剂度他雄胺对大鼠前列腺收缩及α1肾上腺素受体表达的影响
DOI：
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发表时间：
2012
影响因子：
2
通讯作者：
O. Yokoyama
中科院分区：
文献类型：
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作者：
Dong Wang;X. Zha;Keiko Nagase;Y. Hasegawa;I. Muramatsu;O. Yokoyama
假设/研究目的：良性前列腺增生（BPH）是引起下尿路症状（LUTS）的常见原因，在老年男性人群中发病率较高。使用α - 1肾上腺素能拮抗剂和/或5 - α还原酶抑制剂治疗BPH引起的LUTS是一线治疗方法。α -肾上腺素能拮抗剂坦索罗辛对排尿功能障碍的疗效是由于其对BPH患者功能性阻塞的影响。alpha1-肾上腺素能受体在前列腺平滑肌收缩中起重要作用，这是使用alpha1-肾上腺素能拮抗剂治疗功能性梗阻的主要原因。坦索罗辛可与度他雄胺联合使用，以实现快速发作的症状缓解，大多数患者在坦索罗辛退出联合治疗后仍能维持症状缓解。然而，许多基线症状相对严重的患者在停用坦索罗辛后报告其症状恶化。杜他雄胺可抑制5 -还原酶同工酶，使血清双氢睾酮几乎完全抑制，从而使前列腺体积减小，相应改善排尿问题。据我们所知，杜他雄胺引起的雄激素水平改变对α 1-肾上腺素能受体的影响尚未见报道，而α 1-肾上腺素能受体的改变可能导致药物治疗的意外效果。本研究旨在阐明度他雄胺对大鼠前列腺α 1-肾上腺素能受体表达及相关收缩的影响，为5α -还原酶抑制剂与α 1-肾上腺素能拮抗剂联合治疗提供更好的指导。
Hypothesis / aims of study Benign prostatic hyperplasia (BPH) is a frequent cause of lower urinary tract symptoms (LUTS), with a high prevalence in the aging male population. Medical management of LUTS due to BPH with alpha1-adrenergic antagonists and/or 5alpha-reductase inhibitors is the first-line treatment. The efficacy of alpha1-adrenergic antagonist tamsulosin on voiding dysfunction is due to its influence on functional obstruction in BPH patients. Alpha1-adrenergic receptors play a major role in smooth muscle contraction of the prostate, which is the main reason for using alpha1-adrenergic antagonists for functional obstruction. Tamsulosin can be used in combination with dutasteride to achieve rapid onset of symptom relief, which is maintained in the majority of patients after tamsulosin is removed from the combination therapy. However, many patients with relative severe baseline symptoms reported a worsening of their symptoms after the withdrawal of tamsulosin [1]. Dutasteride can inhibit both isoenzymes of 5alpha-reductase and results in near-complete suppression of serum dihydrotestosterone, which causes the reduction in prostate volume and corresponding improvement of voiding problems. To our knowledge, there has not been any report on the influence of dutasteride-induced change of androgen levels on alpha1-adrenergic receptors responsible for functional obstruction, which might lead to unexpected effects of medical treatment. In this study, we try to elucidate the effects of dutasteride on the expression of alpha1-adrenergic receptors and relevant contraction in rat prostate to provide a better guidance for combination treatment with 5alpha-reductase inhibitor and alpha1-adrenergic antagonist.
量化受体特性：组织片段结合方法 - 天然受体药理学分析的强大工具。
DOI：
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发表时间：
2005
期刊：
J. Pharmacol. Sci. 98
影响因子：
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作者：
Muramatsu I.;Tanaka T.;Suzuki F.;Zhang L.;Hiraizumi-Hiraoka Y.;Anisuzzaman A.S.M.;Yamamoto H.;Horinouchi T.;Morishima S.
通讯作者：
Morishima S.