The effects of flavoxate hydrochloride on voltage-dependent L-type Ca2+ currents in human urinary bladder.
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 microM), 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 alpha(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.
Tomoda
Toshihisa
T
Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Aishima
Manami
M
Takano
Naruaki
N
Nakano
Toshiaki
T
Seki
Narihito
N
Yonemitsu
Yoshikazu
Y
Sueishi
Katsuo
K
Naito
Seiji
S
Ito
Yushi
Y
Teramoto
Noriyoshi
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001464:Barium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000502:physiology; D005422:Flavoxate / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D010276:Parasympatholytics / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D010276:Parasympatholytics; D001464:Barium; D005422:Flavoxate; D011188:Potassium