TY - JOUR
T1 - The effects of flavoxate hydrochloride on voltage-dependent L-type Ca 2+ currents in human urinary bladder
AU - Tomoda, Toshihisa
AU - Aishima, Manami
AU - Takano, Naruaki
AU - Nakano, Toshiaki
AU - Seki, Narihito
AU - Yonemitsu, Yoshikazu
AU - Sueishi, Katsuo
AU - Naito, Seiji
AU - Ito, Yushi
AU - Teramoto, Noriyoshi
PY - 2005
Y1 - 2005
N2 - 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 μM), and shifted the steady-state inactivation curve of Ba 2+ currents to the left at a holding potential of -90mV. Immunohistochemical studies indicated the presence of the α 1c subunit protein, which is a constituent of human L-type Ca 2+ channels (Ca v1-2), 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.
AB - 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 μM), and shifted the steady-state inactivation curve of Ba 2+ currents to the left at a holding potential of -90mV. Immunohistochemical studies indicated the presence of the α 1c subunit protein, which is a constituent of human L-type Ca 2+ channels (Ca v1-2), 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.
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U2 - 10.1038/sj.bjp.0706284
DO - 10.1038/sj.bjp.0706284
M3 - Article
C2 - 15965499
AN - SCOPUS:30644460756
SN - 0007-1188
VL - 146
SP - 25
EP - 32
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 1
ER -