Alternative Titleヒト内肛門括約筋収縮に寄与するアドレナリンα₁受容体サブタイプの解明
Periodical titleJournal of pharmacological sciences
Note (General)type:Thesis
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 pEC₅₀ values with SEM of phenylephrine in IAS (6.30 ± 0.13) were higher than those of IMA (5.60 ± 0.10). Furthermore, the age-related pEC₅₀ change 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 pKв value of silodosin, BMY-7378 and prazosin was 9.36 ± 0.53, 7.28 ± 0.20 and 8.89 ± 0.12, respectively. These pKв values and gene expression studies indicated that α₁ᴀ-adrenoceptor subtypes predominantly contributed to human IAS contraction.
博士(医学)・乙第1372号・平成28年3月15日
© 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese PharmacologicalSociety. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
identifier:Journal of pharmacological sciences Vol.127 No.4 p.424-429(2015.04)
identifier:13478613
identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3193
identifier:Journal of pharmacological sciences, 127(4): 424-429
DOIinfo:doi/10.1016/j.jphs.2015.02.016
Collection (particular)国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
Date Accepted (W3CDTF)2016-05-01T16:38:40+09:00
Data Provider (Database)国立国会図書館 : 国立国会図書館デジタルコレクション