オバラ　ケイスケ   Obara Keisuke   小原　圭将    所属   東邦大学  薬学部 薬学科    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Effects of distigmine on electrical field stimulation-induced contraction of mouse urinary bladder smooth muscles
掲載誌名	正式名：Pharmacology 略　 称：Pharmacology ISSNコード：00317012/14230313
出版社	Karger
巻・号・頁	99(3-4),pp.106-113
著者・共著者	Obara K†, Kobayashi Y†, Chino D†, Tanaka Y＊†
担当区分	筆頭著者
発行年月	2017/03
概要	Distigmine bromide (distigmine), a reversible carbamate cholinesterase (ChE) inhibitor, is indicated in Japan for detrusor underactivity, myasthenia gravis, and glaucoma. Although there is clinical evidence for the effectiveness of distigmine in the treatment of detrusor underactivity, mechanisms by which distigmine restores impaired urinary bladder smooth muscle (UBSM) contractility have not been fully investigated. The aims of the present study were to investigate the potentiating effects of distigmine on UBSM contractions in response to parasympathetic nerve stimulation induced by electrical field stimulation (EFS) in mice. In isolated mouse UBSM, EFS (1–16 Hz) produced tetrodotoxin (TTX)-sensitive, frequency-dependent contractions. The contractile responses to EFS were largely attenuated by atropine (10-6 M). UBSM contractility that remained in the presence of atropine was nearly abolished by the addition of α,β-methylene adenosine triphosphate (α,β-mATP) (10-4 M). Distigmine (3 × 10-7 M) significantly potentiated EFS-induced contractile responses engendered in the presence of α,β-mATP (10-4 M), but not atropine (10-6 M). These findings indicate that distigmine powerfully potentiates UBSM contractions selectively induced by parasympathetic nerve-derived acetylcholine (ACh), demonstrating a potential mechanism by which it stimulates detrusor contractile function.