Inhibitory mechanism of monensin on high K+-induced contraction in guniea-pig urinary bladder.
Journal of pharmacological sciences 2006 Feb 1; 100(2):133-41
Kaneda T, Takeuchi M, Shimizu K, Urakawa N, Nakajyo S, Mochizuki-Kobayashi M, Ueda F, Hondo R
Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University, Musashino, Tokyo, Japan. t-kaneda@nvau.ac.jp
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.