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Molecular Pharmacology

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Abstract

Direct inhibition of inositol-1,4,5-trisphosphate-induced Ca2+ release from brain microsomes by K+ channel blockers.

P Palade, C Dettbarn, P Volpe, B Alderson and A S Otero
Molecular Pharmacology October 1989, 36 (4) 664-672;
P Palade
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C Dettbarn
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P Volpe
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B Alderson
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A S Otero
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Abstract

Tetraethylammonium and 9-tetraethylammonium have previously been reported to inhibit inositol-1,4,5-trisphosphate (IP3)-induced Ca2+ release from brain microsomes, purportedly by blocking potassium channels [Biochem. J. 258:617-620 (1988)]. The effects of these and other K+ channel blockers have been studied here in greater detail using a spectrophotometric assay for Ca2+ movements into and out of canine brain microsomes. IP3-induced Ca2+ release was inhibited by substitution of K+ in the medium with nominally impermeant cations or by addition of most of the K+ channel blockers tested. Nevertheless, addition of valinomycin to the medium (to provide an alternative pathway for counter-ion K+ movements) failed to alleviate the inhibition of IP3-induced Ca2+ release caused by K+ channel blockers. To determine whether these substances act by inhibition of IP3 binding or by direct interaction with the Ca2+ channel of the internal store that promotes IP3-induced Ca2+ release, their effect on [3H]IP3 binding was investigated. None of the K+ channel blockers tested inhibited [3H]IP3 binding. Nearly all the K+ channel blockers appear to interact directly with a Ca2+ channel of the intracellular stores or perhaps interfere with its coupling to the IP3 receptor. Because of their multiplicity of actions, these substances cannot be presumed to be either selective K+ channel blockers or selective inhibitors of IP3-induced Ca2+ release from internal stores. Three of them were even found to partially inhibit valinomycin-stimulated 86Rb uptake into liposomes.

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Molecular Pharmacology
Vol. 36, Issue 4
1 Oct 1989
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Abstract

Direct inhibition of inositol-1,4,5-trisphosphate-induced Ca2+ release from brain microsomes by K+ channel blockers.

P Palade, C Dettbarn, P Volpe, B Alderson and A S Otero
Molecular Pharmacology October 1, 1989, 36 (4) 664-672;

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Abstract

Direct inhibition of inositol-1,4,5-trisphosphate-induced Ca2+ release from brain microsomes by K+ channel blockers.

P Palade, C Dettbarn, P Volpe, B Alderson and A S Otero
Molecular Pharmacology October 1, 1989, 36 (4) 664-672;
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