鉴定α1-肾上腺素受体亚型介导人离体输尿管收缩的作用。

Characterization of α1-adrenoceptor subtypes mediating contraction in human isolated ureters.

机构信息

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.

出版信息

Urology. 2011 Mar;77(3):762.e13-7. doi: 10.1016/j.urology.2010.09.034. Epub 2010 Dec 31.

DOI:10.1016/j.urology.2010.09.034

PMID:21195469

Abstract

OBJECTIVES

To characterize the contractile functions of the α(1)-adrenoceptor (AR) subtypes present in the human ureter.

METHODS

Specimens were taken from patients with renal cancer ("upper ureters;" n = 51) or bladder cancer ("lower ureters;" n = 23) who had not been treated by chemotherapy, radiation therapy, or immunotherapy before surgery. Patients systemically taking an α(1)-AR agonist or antagonist were excluded from this study. The effects of α(1)-AR antagonists against phenylephrine (α(1)-AR agonist)-induced contractions were evaluated in human isolated ureteral preparations.

RESULTS

Pooled data from all ureters showed that phenylephrine (α(1)-AR agonist) induced a concentration-dependent tonic contraction (pD(2) value, 4.92 ± 011). The phenylephrine-induced maximum contraction was significantly greater in lower ureters than in upper ones. Prazosin (nonselective α(1)-AR antagonist), silodosin (selective α(1A)-AR antagonist), and BMY-7378 (selective α(1D)-AR antagonist) all shifted the concentration-contractile response curve for phenylephrine to the right, the rank order of potencies in all ureters (pK(B) values) being silodosin (9.72 ± 0.14) > prazosin (8.64 ± 0.08) > BMY-7378 (7.04 ± 0.14). The α(1A)-AR antagonist silodosin was thus much more potent than the other 2 antagonists.

CONCLUSIONS

Our results suggest that among α(1)-ARs, the α(1A) subtype plays the major role in contraction in the human ureter.

摘要

目的

描述存在于人类输尿管中的α(1)-肾上腺素受体 (AR) 亚型的收缩功能。

方法

标本取自未接受化疗、放疗或免疫治疗的肾癌（“上输尿管”；n = 51）或膀胱癌（“下输尿管”；n = 23）患者。系统性使用α(1)-AR 激动剂或拮抗剂的患者被排除在本研究之外。在人类离体输尿管标本中评估了 α(1)-AR 拮抗剂对去氧肾上腺素（α(1)-AR 激动剂）诱导收缩的作用。

结果

所有输尿管的汇总数据显示，去氧肾上腺素（α(1)-AR 激动剂）诱导浓度依赖性紧张性收缩（pD2 值为 4.92 ± 011）。下输尿管的去氧肾上腺素诱导的最大收缩明显大于上输尿管。哌唑嗪（非选择性 α(1)-AR 拮抗剂）、西洛多辛（选择性 α(1A)-AR 拮抗剂）和 BMY-7378（选择性 α(1D)-AR 拮抗剂）均使去氧肾上腺素的浓度-收缩反应曲线右移，所有输尿管的效力顺序（pK（B）值）为西洛多辛（9.72 ± 0.14）>哌唑嗪（8.64 ± 0.08）>BMY-7378（7.04 ± 0.14）。因此，α(1A)-AR 拮抗剂西洛多辛比其他 2 种拮抗剂的效力要强得多。