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.