Inhibitory mechanism of monensin on high K+-induced contraction in guniea-pig urinary bladder.
In this study, we examined the inhibitory mechanism of monensin on high K+-induced contraction in guinea-pig urinary bladder. The relaxant effect of monensin (0.001 - 10 microM) was more potent than those of NaCN (100 microM - 1 mM) and forskolin (3 - 10 microM). Monensin (0.1 microM), NaCN (300 microM), or forskolin (10 microM) inhibited high K+-induced contraction without decreasing [Ca2+]i level. Monensin and NaCN remarkably decreased creatine phosphate and ATP contents. Monensin and NaCN inhibited high K+-induced increases in flavoprotein fluorescence, which is involved in mitochondrial respiration. Forskolin increased cAMP content but monensin did not. Monensin increased Na+ content at 10 microM but not at 0.1 microM that induced maximum relaxation. In the alpha-toxin-permeabilized muscle, forskolin significantly inhibited the Ca2+-induced contraction, but monensin did not affect it. These results suggest that the relaxation mechanism of monensin in smooth muscle of urinary bladder may be an inhibition of oxidative metabolism.
Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University, Musashino, Tokyo, Japan. t-kaneda@nvau.ac.jp
Takeharu
T
Kaneda
Mayumi
M
Takeuchi
Kazumasa
K
Shimizu
Norimoto
N
Urakawa
Shinjiro
S
Nakajyo
Mariko
M
Mochizuki-Kobayashi
Fukiko
F
Ueda
Ryo
R
Hondo
D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism; D005456:Fluorescent Dyes; D006168:Guinea Pigs; D007537:Isometric Contraction / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008985:Monensin / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010725:Phosphocreatine / Q000032:analysis / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology*; D012964:Sodium / Q000032:analysis / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism
D005456:Fluorescent Dyes; D010725:Phosphocreatine; D005576:Colforsin; D000255:Adenosine Triphosphate; D008985:Monensin; D012964:Sodium; D000242:Cyclic AMP; D011188:Potassium; D002118:Calcium