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

Eur J Pharmacol. 2003 Dec 15;482(1-3):287-95. doi: 10.1016/j.ejphar.2003.09.068.

Abstract

We have investigated the effects of MCC-134 (1-[4-(1H-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 microM). The MCC-134 (30 microM)-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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / physiology*
  • Animals
  • Dose-Response Relationship, Drug
  • Female
  • Imidazoles / pharmacology*
  • In Vitro Techniques
  • Muscle Relaxation / drug effects
  • Muscle Relaxation / physiology
  • Potassium Channels / agonists
  • Potassium Channels / physiology*
  • Swine
  • Thioamides / pharmacology*
  • Urethra / drug effects*
  • Urethra / physiology

Substances

  • Imidazoles
  • MCC 134
  • Potassium Channels
  • Thioamides
  • Adenosine Triphosphate