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The involvement of potassium channels in the action of ciclazindol in rat portal vein
Author(s) -
Noack Th.,
Edwards G.,
Deitmer P.,
Greengrass P.,
Morita T.,
Andersson P.O.,
Criddle D.,
Wyllie M. G.,
Weston A.H.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14286.x
Subject(s) - portal vein , potassium channel , potassium , action (physics) , neuroscience , chemistry , anatomy , pharmacology , medicine , biology , physics , organic chemistry , quantum mechanics
1 In whole portal veins, ciclazindol (0.3–10 μ m ) increased the amplitude and duration, but decreased the frequency of spontaneous contractions. Glibenclamide (0.3–10 μ m ) produced a small increase in contraction amplitude and duration with a small reduction in contraction frequency. 2 In whole portal veins, ciclazindol (1–10 μ m ) antagonized the relaxant effects of BRL 38227 in a non‐competitive manner. Under identical conditions, the effects of glibenclamide (0.3–10 μ m ) appeared to be competitive. 3 In whole portal veins loaded with 42 K, ciclazindol itself (up to 3 μ m ) had no detectable effect on basal 42 K exchange. However, the increase in 42 K efflux produced by BRL 38227 (5 μ m ) was antagonized by ciclazindol (3 μ m ). Similar effects were produced by glibenclamide (up to 3 μ m ). 4 In freshly‐isolated portal vein cells examined by the whole‐cell voltage‐clamp technique, ciclazindol (1–100 μ m ) inhibited the slowly‐activating and inactivating transient outward current ( I TO ) which could be generated at potentials more positive than −30 mV. In addition ciclazindol (1–10 μ m ) inhibited the non‐inactivating K‐current ( I KCO ) induced by BRL 38227 (10 μ m ). 5 In freshly‐isolated portal vein cells under current‐clamp conditions, the hyperpolarization produced by BRL 38227 (10 μ m ) was reversed by ciclazindol (1–10 μ m ). 6 In porcine brain membrane fragments, glibenclamide (0.65 n m ) displaced 50% of the binding of [ 3 H]‐glibenclamide whereas ciclazindol (up to 10 μ m ) had no effect. 7 It is concluded that ciclazindol is a K‐channel blocker. Its action is not selective for the channel(s) which carry I KCO but also extends to those which carry I TO . Its inability to displace [ 3 H]‐glibenclamide from porcine brain fragments may indicate that antagonism of BRL 38227 by ciclazindol in smooth muscle is exerted at a site different from that of glibenclamide.