タナカ　ヨシオ   Tanaka Yoshio   田中　芳夫    所属   東邦大学  薬学部 薬学科    職種   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	Effect of distigmine on the contractile response of guinea pig urinary bladder to electrical field stimulation.
掲載誌名	正式名：European journal of pharmacology 略　 称：Eur J Pharmacol ISSNコード：00142999
掲載区分	国外
出版社	ELSEVIER SCIENCE BV
巻・号・頁	809,pp.209-214
著者・共著者	Obara K†, Kobayashi Y†, Chino D†, Tanaka Y＊†
担当区分	最終著者,責任著者
発行年月	2017/05
概要	Distigmine bromide (distigmine) is a reversible carbamate group cholinesterase (ChE) inhibitor. Although mainly used clinically for the treatment of myasthenia gravis, distigmine is also indicated for detrusor underactivity in Japan. According to the pharmacological classification of distigmine, its therapeutic effect against detrusor underactivity appears to be produced by enhanced urinary bladder smooth muscle (UBSM) contractility due to an increased concentration of acetylcholine between parasympathetic nerve endings and UBSM cells. However, ATP as well as acetylcholine is also released from parasympathetic nerve endings that dominate UBSM. The present study was thus carried out to investigate the potentiating effects of distigmine on the two UBSM contractile components in response to parasympathetic nerve stimulation induced by electrical field stimulation (EFS). In isolated guinea pig UBSM tissues, EFS (1–16 Hz) produced tetrodotoxin-sensitive, frequency-dependent contractions. The contractile responses to EFS were largely diminished by atropine (10⁠−6 M), and the remaining contractile components in the presence of atropine were virtually abolished by α,β-methylene adenosine triphosphate (α,β-mATP) (10⁠−4 M). Distigmine (10⁠−6 M) significantly potentiated EFS-induced contractile components generated in the presence of α,β-mATP (10⁠−4 M), but did not potentiate EFS-induced contractile components generated in the presence of atropine (10⁠−6 M). These findings clearly indicate that distigmine strongly potentiates UBSM contraction selectively induced by parasympathetic nerve-derived acetylcholine, suggesting a potential mechanism by which distigmine restores detrusor underactivity.