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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3193

Title: Characterizations of the α₁-adrenoceptor subtypes mediating contractions of the human internal anal sphincter.
Other Titles: 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
Authors: Owaki, Hiroyuki
Sadahiro, Sotaro
Takaki, Miyako
大脇, 浩幸
貞廣, 荘太郎
高木, 都
Keywords: Human internal anal sphincter
α₁-adrenoceptor
Fecal incontinence
Age-related response change
Comparison with inferior mesenteric artery
As a predictor of systemic arterial pressure
Issue Date: Apr-2015
Publisher: Elsevier
Citation: Journal of pharmacological sciences Vol.127 No.4 p.424-429(2015.04)
Abstract: 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.
Description: 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 Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
URI: http://hdl.handle.net/10564/3193
ISSN: 13478613
Academic Degrees and number: 24601B1372
Degree-granting date: 2016-03-15
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2015年度

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