Disruption of the actin cytoskeleton abolishes high affinity 3H-glibenclamide binding in rat aortic rings.
The interaction between the cytoskeleton and the ATP-sensitive K+ channel (KATP channel) was studied in rat aortic rings by examining the binding of the sulphonylurea blocker, 3H-glibenclamide, and of the opener, 3H-P1075. The actin cytoskeleton disrupting agents, cytochalasin D (1 microM) and latrunculin B (1 microM), abolished the high affinity component of 3H-glibenclamide binding. Preincubation with the actin cytoskeleton stabilizing agent, phalloidin (10 microM) prevented the effect of cytochalasin D. In contrast, binding of the opener, 3H-P1075, and inhibition of this binding by glibenclamide, were unaffected by cytochalasin D (3 microM). Colchicine (100 microM), which disassembles microtubules, had no effect on the binding of 3H-glibenclamide and 3H-P1075. The data show that high affinity binding of glibenclamide, which mediates the effects of the sulphonylurea in this preparation, requires the presence of an intact actin cytoskeleton. Binding of the opener is unaffected by the state of the cytoskeleton and preserves a conformational state in which high affinity binding of glibenclamide to the sulphonylurea receptor can occur.
Löffler-Walz
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Department of Pharmacology, Medical Faculty, University of Tübingen, Germany.
Quast
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D000199:Actins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005905:Glyburide / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010590:Phalloidine / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000819:agonists / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D014665:Vasodilator Agents / Q000494:pharmacology
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006146:Guanidines; D019384:Nucleic Acid Synthesis Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011725:Pyridines; D013844:Thiazoles; D053778:Thiazolidines; D014665:Vasodilator Agents; D010590:Phalloidine; D015638:Cytochalasin D; C073896:N-cyano-N'-(1,1-dimethylpropyl)-N''-(3-pyridinyl)guanidine; D000255:Adenosine Triphosphate; C037068:latrunculin B; D005905:Glyburide