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OtherCELLULAR AND MOLECULAR PHARMACOLOGY

Nicorandil Activates Glibenclamide-Sensitive K+Channels in Smooth Muscle Cells of Pig Proximal Urethra

Noriyoshi Teramoto and Alison F. Brading
Journal of Pharmacology and Experimental Therapeutics January 1997, 280 (1) 483-491;
Noriyoshi Teramoto
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Alison F. Brading
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Abstract

The effects of nicorandil on ionic currents recorded from single smooth muscle cells of pig proximal urethra were investigated using patch-clamp techniques. Tension measurement was also performed to study the effects of nicorandil on the resting tone of pig urethra. Nicorandil produced a concentration-dependent sustained outward current that was suppressed by glibenclamide at −50 mV and was carried selectively by K+. In cell-attached configuration, nicorandil activated a 43-pS K+ channel that was reversibly inhibited by 10 μM glibenclamide. This glibenclamide-sensitive 43-pS K+ channel (KGS) “ran down” after excision of the membrane patch. In inside-out configuration, the application of either 1 mM Mg-ATP or 1 mM nucleotide diphosphate reactivated the KGS. In symmetrical 140 mM K+ conditions, 300 μM nicorandil and 300 μM levcromakalim activated a 2.14-pA K+ channel that exhibited the same amplitude and similar channel-opening kinetics. Methylene blue (10–100 μM), a soluble guanylate cyclase inhibitor, did not inhibit the opening of the nicorandil-induced KGS. The KGS was not activated by either sodium nitroprusside (10–100 μM) or 8-bromo guanosine 3′:5′-cyclic monophosphate (1 mM). Nicorandil caused a concentration-dependent relaxation of the urethral resting tone but was less potent than levcromakalim. The relaxation induced by 10 μM nicorandil was partially inhibited by glibenclamide (1–10 μM) and also by methylene blue (10–100 μM). These results indicate that two independent nicorandil-induced relaxation mechanisms may be present in pig urethra.

Footnotes

  • Send reprint requests to: Noriyoshi Teramoto, the University Department of Pharmacology, Mansfield Road, Oxford, OX1 3QT, U.K.

  • ↵1 This work was supported by the Wellcome Trust.

  • Abbreviations:
    SNP
    sodium nitroprusside
    KGS
    glibenclamide-sensitive 43-pS K+ channel
    KATP
    ATP-sensitive K+ channel
    KCOs
    potassium channel openers
    4-AP
    4-aminopyride
    TEACl
    tetraethylammonium chloride
    NDPs
    nucleotide diphosphates
    BSA
    bovine serum albumin
    PSS
    physiological salt solution
    EGTA
    ethylene glycol-bis (β-aminoethylether) N,N,N′,N′-tetraacetic acid
    Tris
    Tris (hydroxymethyl) methylammonium chloride
    GDP
    guanosine 5′-diphosphate
    IDP
    inosine 5′-diphosphate
    NO
    nitric oxide
    DMSO
    dimethylsulfoxide
    EK
    potassium equilibrium potential
    • Received April 8, 1996.
    • Accepted September 13, 1996.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 280, Issue 1
1 Jan 1997
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OtherCELLULAR AND MOLECULAR PHARMACOLOGY

Nicorandil Activates Glibenclamide-Sensitive K+Channels in Smooth Muscle Cells of Pig Proximal Urethra

Noriyoshi Teramoto and Alison F. Brading
Journal of Pharmacology and Experimental Therapeutics January 1, 1997, 280 (1) 483-491;

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OtherCELLULAR AND MOLECULAR PHARMACOLOGY

Nicorandil Activates Glibenclamide-Sensitive K+Channels in Smooth Muscle Cells of Pig Proximal Urethra

Noriyoshi Teramoto and Alison F. Brading
Journal of Pharmacology and Experimental Therapeutics January 1, 1997, 280 (1) 483-491;
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