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The effects of flavoxate hydrochloride on voltage‐dependent L‐type Ca 2+ currents in human urinary bladder
Author(s) -
Tomoda Toshihisa,
Aishima Manami,
Takano Naruaki,
Nakano Toshiaki,
Seki Narihito,
Yonemitsu Yoshikazu,
Sueishi Katsuo,
Naito Seiji,
Ito Yushi,
Teramoto Noriyoshi
Publication year - 2005
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706284
Subject(s) - nifedipine , endocrinology , medicine , chemistry , contraction (grammar) , detrusor muscle , muscle contraction , patch clamp , urinary bladder , electrophysiology , calcium
The effects of flavoxate hydrochloride (Bladderon®, piperidinoethyl‐3‐methylflavone‐8‐carboxylate; hereafter referred as flavoxate) on voltage‐dependent nifedipine‐sensitive inward Ba 2+ currents in human detrusor myocytes were investigated using a conventional whole‐cell patch‐clamp. Tension measurement was also performed to study the effects of flavoxate on K + ‐induced contraction in human urinary bladder. Flavoxate caused a concentration‐dependent reduction of the K + ‐induced contraction of human urinary bladder. In human detrusor myocytes, flavoxate inhibited the peak amplitude of voltage‐dependent nifedipine‐sensitive inward Ba 2+ currents in a voltage‐ and concentration‐dependent manner ( K i =10 μ M ), and shifted the steady‐state inactivation curve of Ba 2+ currents to the left at a holding potential of −90 mV. Immunohistochemical studies indicated the presence of the α 1C subunit protein, which is a constituent of human L‐type Ca 2+ channels (Ca V 1.2), in the bundles of human detrusor smooth muscle. These results suggest that flavoxate caused muscle relaxation through the inhibition of L‐type Ca 2+ channels in human detrusor.British Journal of Pharmacology (2005) 146 , 25–32. doi: 10.1038/sj.bjp.0706284