title: Effects of Distigmine on Electrical Field Stimulation-Induced Contraction of Mouse Urinary Bladder Smooth Muscles.
abstract: Distigmine bromide (distigmine), a reversible carbamate cholinesterase inhibitor, is used in Japan for treating detrusor underactivity, myasthenia gravis, and glaucoma. Although there is clinical evidence about 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 this 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-sensitive, frequency-dependent contractions. The contractile responses to EFS were largely attenuated by atropine (10-6 mol/l). UBSM contractility that occurred in the presence of atropine was nearly eliminated by the addition of α,β-methylene adenosine triphosphate (α,β-mATP, 10-4 mol/l). Distigmine (3 × 10-7 mol/l) significantly potentiated EFS-induced contractile responses engendered in the presence of α,β-mATP (10-4 mol/l), but not atropine (10-6 mol/l). These findings indicate that distigmine powerfully potentiates UBSM contractions selectively induced by parasympathetic nerve-derived acetylcholine, thereby demonstrating a potential mechanism by which it stimulates detrusor contractile function.
authors: Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University Miyama, Funabashi, Japan.
authors: Keisuke
authors: K
authors: Obara
authors: Yurina
authors: Y
authors: Kobayashi
authors: Daisuke
authors: D
authors: Chino
authors: Yoshio
authors: Y
authors: Tanaka
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004558:Electric Stimulation / Q000379:methods; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques; D011726:Pyridinium Compounds / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
chemical_list: D002800:Cholinesterase Inhibitors; D011726:Pyridinium Compounds; C084645:distigmine