Comparative Studies on the Relaxing Action of Several Adenosine 5'-Triphosphate-Sensitive K^+ Channel Openers in Pig Urethra
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概要
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The relaxing effects of the adenosine 5'-triphosphate (ATP)-sensitive K^+ channel openers (K_<ATP> openers; diazoxide, minoxidil, pinacidil, (±)-cromakalim, (+)-cromakalim and (-)-cromakalim) were investigated on the resting tone of pig proximal urethra. In addition, patch-clamp techniques were utilized for recording cromakalim-induced ionic currents in cells dispersed from the same urethral region. The (-)-cromakalim-induced relaxation of urethral muscle strips was stable, reversible and reproducible. The rank order of potency regarding of K_<ATP> openers in lowering the resting urethral tone was (-)-cromakalim > pinacidil > diazoxide > minoxidil. K_<ATP> opener-induced urethral relaxation was suppressed by subsequent application of glibenclamide (1μM). (+)-Cromakalim (≤10 μM) did not relax the urethra nor antagonize the (-)-cromakalim-induced urethral relaxation. However, at higher concentrations, (+)-cromakalim (≥30μM) caused a small but significant urethral relaxation. In accordance with these observations, the relaxation induced by 5μM (-)-cromakalim was identical to that induced by 10 μM (±)-cromakalim, as expected from a theoretical half potency for (±)-cromakalim. In whole-cell recording, (-)-cromakalim and (+)-cromakalim (100μM) activated a glibenclamide-sensitive out-ward current which was due to the activation of the glibenclamide-sensitive 43pS K^+ channel (K_<GS>-43 pS). The potency of (+)-cromakalim to activate K_<GS>-43 pS was much weaker than that of (-)-cromakalim. These results indicate that the ability of K_<ATP> openers to relax pig urethral smooth muscle can be accounted for by activation of gliben-clamide-sensitive K^+ channels.
- 日本平滑筋学会の論文
著者
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Ito Yushi
Department Of Pharmacology Faculty Of Medicine Kyushu University
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Ito Yushi
Department Of Neonatology National Center For Child Health And Development
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TERAMOTO Noriyoshi
Department of Pharmacology, Faculty of Medicine, Kyushu University
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Teramoto Noriyoshi
Department Of Pharmacology Faculty Of Medicine Kyushu University
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Ito Yushi
Department of Health Science, Kumamoto Health Science University
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