The effects of MCC-134 on the ATP-sensitive K + channels in pig urethra

• Published in: European journal of pharmacology 2003-12, Vol.482 (1), p.287-295
• Main Authors: Yunoki, Takakazu, Teramoto, Noriyoshi, Takano, Naruaki, Seki, Narihito, Creed, Kate E., Naito, Seiji, Ito, Yushi
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - physiology; Animals; ATP-sensitive; Biological and medical sciences; Dose-Response Relationship, Drug; Female; Imidazoles - pharmacology; In Vitro Techniques; K + channel; MCC-134; Medical sciences; Muscle Relaxation - drug effects; Muscle Relaxation - physiology; Pharmacology. Drug treatments; Potassium Channels - agonists; Potassium Channels - physiology; Smooth muscle; Sulphonylurea receptor; Swine; Thioamides - pharmacology; Urethra; Urethra - drug effects; Urethra - physiology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2003.09.068

We have investigated the effects of MCC-134 (1-[4-(1 H-imidazol-1-yl)benzoyl]- N-methyl-cyclobutanecarbothioamide) on membrane currents and ATP-sensitive K + channel (K ATP channel) opener-induced currents in pig urethra by use of patch-clamp techniques (conventional whole-cell configuration and nystatin perforated patch recordings). Tension measurement was also performed to study the effects of MCC-134 on the resting tone of pig urethral strips. MCC-134 reduced the resting tone of pig urethra in a concentration-dependent manner (EC 50=6 μM). The MCC-134 (30 μM)-induced relaxation was suppressed by glibenclamide. In voltage-clamp experiments, MCC-134 produced a concentration-dependent inward K + current which was suppressed by application of glibenclamide at a holding potential of −50 mV (symmetrical 140 mM K + conditions). Application of MCC-134 enhanced diazoxide-induced inward currents and inhibited pinacidil-induced inward currents in a concentration-dependent manner at −50 mV. These results suggest that MCC-134 induces glibenclamide-sensitive K ATP currents in pig urethra.