Characterizations of the α1-adrenoceptor subtypes mediating contractions of the human internal anal sphincter.

Characterizations of the α1-adrenoceptor subtypes mediating contractions of the human internal anal sphincter.
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介导人肛门内括约肌收缩的 α1-肾上腺素受体亚型的特征。

DOI:
10.1016/j.jphs.2015.02.016
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发表时间:
2015
期刊:
影响因子:
3.5
通讯作者:
Takaki M
Takaki M
中科院分区:
医学3区
文献类型:
--
作者:
Owaki H;Sadahiro S;Takaki M

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人的肛门内括约肌受α1肾上腺素能受体的刺激而收缩,因此α1肾上腺素能受体激动剂可用于治疗大便失禁。本研究描述了α1受体亚型在人免疫球蛋白收缩中的作用,并探讨了大便失禁患者的年龄相关风险。对11例患者进行IAS和肠系膜下动脉(IMA)检测,作为体动脉压的预测指标。在不同亚型选择性α1肾上腺素受体拮抗剂存在的情况下,用苯肾上腺素等长收缩实验对两条肌条进行评估。对同一样本进行免疫组织化学和基因表达研究。扫描电子显微镜显示IAS患者苯肾上腺素的pEC50值(6.30±0.13)高于IMA患者(5.60±0.10)。此外,IAS的pEC50在70岁和70岁≥之间的变化与年龄相关(分别为6.58±0.13和6.07±0.16,P<0.05)。在间接免疫吸附实验中,三种α1受体拮抗剂均使去氧肾上腺素的量效曲线右移。西洛多辛、BMY-7378和哌唑嗪的pKB值分别为9.36±0.53、7.28±0.20和8.89±0.12。这些pKB值和基因表达研究表明,α1A-肾上腺素能受体亚型对人IAS收缩起主要作用。
Human internal anal sphincter (IAS) is contracted by α1-adrenoceptor stimulation and thus α1-adrenoceptor agonists may be useful in treating fecal incontinence. This study characterizes the contribution of α1-adrenoceptor subtypes in contraction of human IAS and to investigate the age-related risk of patients with fecal incontinence. IAS and inferior mesenteric artery (IMA), as a predictor of systemic arterial pressure, were obtained from 11 patients. Both muscle strips were assessed by isometric-contraction experiments using phenylephrine, further in IAS, in the presence of various subtype selective α1-adrenoceptor antagonists. Immunohistochemistry and gene expression studies were performed in the same samples. The mean pEC50values with SEM of phenylephrine in IAS (6.30 ± 0.13) were higher than those of IMA (5.60 ± 0.10). Furthermore, the age-related pEC50change of IAS was observed between age <70 and ≥70 (6.58 ± 0.13 and 6.07 ± 0.16, respectively (P< 0.05)). In IAS, rightward shift of the concentration–response curves of phenylephrine was observed with three α1-adrenoceptor antagonists. Each pKBvalue of silodosin, BMY-7378 and prazosin was 9.36 ± 0.53, 7.28 ± 0.20 and 8.89 ± 0.12, respectively. These pKBvalues and gene expression studies indicated that α1A-adrenoceptor subtypes predominantly contributed to human IAS contraction.
局部去氧肾上腺素治疗辐射引起的大便失禁。
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