Ciclazindol inhibits ATP-sensitive K+ channels and stimulates insulin secretion in CR1-G1 insulin-secreting cells

Kevin Lee, R N Khan, I C Rowe, S E Ozanne, A C Hall, E Papadakis, C N Hales, M L Ashford

    Research output: Contribution to journalArticle

    8 Citations (Scopus)

    Abstract

    Ciclazindol, an anorectic drug, was shown to inhibit ATP-sensitive K+ (K(ATP)) channel currents and stimulate insulin secretion from CRI-G1 insulin-secreting cells. In contrast, the structurally related anorectic agent mazindol and the amphetamine-based anorectic compounds diethylpropion, fenfluramine, and phentermine had no effect on K(ATP) channel activity in this cell line. Similarly, cicliazindol elicited insulin secretion from CRI-G1 cells, whereas mazindol had no secretagogue action. The mechanism by which ciclazindol acts to inhibit K(ATP) channel activity is different than that of the sulfonylureas as ciclazindol is effective after procedures that decouple the sulfonylurea receptor from the K(ATP) channel. In agreement with this finding, ciclazindol failed to displace [3H]glibenclamide from CRI-G1 microsomal membranes. Further experiments demonstrated that ciclazindol has no significant effect on voltage-activated currents in this cell line.
    Original languageEnglish
    Pages (from-to)715-20
    Number of pages6
    JournalMolecular Pharmacology
    Volume49
    Issue number4
    Publication statusPublished - Apr 1996

    Keywords

    • Glyburide
    • Indoles
    • Hypoglycemic Agents
    • Cells, Cultured
    • Potassium Channel Blockers
    • Appetite Depressants
    • Adenosine Triphosphate
    • Insulin

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