Tolbutamide excites rat glucoreceptive ventromedial hypothallamic neurones by indirect inhibition of ATP-K+ channels

M. L. Ashford, P. R. Boden, J. M. Treherne

    Research output: Contribution to journalArticle

    123 Citations (Scopus)

    Abstract

    1. The sulphonylureas, tolbutamide (0.1-10 mM) and glibenclamide (0.1-100 microM) shown not to inhibit ATP-K+ channel currents when applied to inside-out membrane patches excised from rat cultured cerebral cortex or freshly-dispersed ventromedial hypothalamic nucleus (VMHN) neurones. 2. Saturable binding sites for [3H]-glibenclamide, with similar affinity constants are present in rat cerebral cortex and hypothalamic membranes. The density of binding sites was lower in the hypothalamus than cortex. 3. Intracellular recordings from glucoreceptive VMHN neurones in hypothalamic slices were obtained. In the absence of glucose, tolbutamide (0.1 mM) depolarized these cells, increased membrane resistance and elicited action potentials. 4. Tolbutamide (0.1 mM) inhibited ATP-K+ channel currents and induced action current activity in cell-attached recordings from glucoreceptive VMHN neurones. 5. Glibenclamide (10-500 nM) had no effect per se on glucoreceptive VMHN neurones but did antagonize the actions of tolbutamide. 6. It is concluded that the hypothalamic (and perhaps cortical) sulphonylurea receptors are not directly coupled to ATP-K+ channels.
    Original languageEnglish
    Pages (from-to)531-540
    Number of pages10
    JournalBritish Journal of Pharmacology
    Volume101
    Issue number3
    Publication statusPublished - Nov 1990

    Fingerprint

    Ventromedial Hypothalamic Nucleus
    Tolbutamide
    Glyburide
    Adenosine Triphosphate
    Neurons
    Cerebral Cortex
    Binding Sites
    Sulfonylurea Receptors
    Membranes
    Hypothalamus
    Action Potentials
    Cell Membrane
    Glucose

    Keywords

    • Rats, Inbred Strains
    • Rats
    • Glyburide
    • Cerebral Cortex
    • Animals
    • Ventromedial Hypothalamic Nucleus
    • Action Potentials
    • Tolbutamide
    • Adenosine Triphosphate
    • Potassium Channels
    • Male
    • Binding Sites

    Cite this

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    title = "Tolbutamide excites rat glucoreceptive ventromedial hypothallamic neurones by indirect inhibition of ATP-K+ channels",
    abstract = "1. The sulphonylureas, tolbutamide (0.1-10 mM) and glibenclamide (0.1-100 microM) shown not to inhibit ATP-K+ channel currents when applied to inside-out membrane patches excised from rat cultured cerebral cortex or freshly-dispersed ventromedial hypothalamic nucleus (VMHN) neurones. 2. Saturable binding sites for [3H]-glibenclamide, with similar affinity constants are present in rat cerebral cortex and hypothalamic membranes. The density of binding sites was lower in the hypothalamus than cortex. 3. Intracellular recordings from glucoreceptive VMHN neurones in hypothalamic slices were obtained. In the absence of glucose, tolbutamide (0.1 mM) depolarized these cells, increased membrane resistance and elicited action potentials. 4. Tolbutamide (0.1 mM) inhibited ATP-K+ channel currents and induced action current activity in cell-attached recordings from glucoreceptive VMHN neurones. 5. Glibenclamide (10-500 nM) had no effect per se on glucoreceptive VMHN neurones but did antagonize the actions of tolbutamide. 6. It is concluded that the hypothalamic (and perhaps cortical) sulphonylurea receptors are not directly coupled to ATP-K+ channels.",
    keywords = "Rats, Inbred Strains, Rats, Glyburide, Cerebral Cortex, Animals, Ventromedial Hypothalamic Nucleus, Action Potentials, Tolbutamide, Adenosine Triphosphate, Potassium Channels, Male, Binding Sites",
    author = "Ashford, {M. L.} and Boden, {P. R.} and Treherne, {J. M.}",
    year = "1990",
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    journal = "British Journal of Pharmacology",
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    }

    Tolbutamide excites rat glucoreceptive ventromedial hypothallamic neurones by indirect inhibition of ATP-K+ channels. / Ashford, M. L.; Boden, P. R.; Treherne, J. M.

    In: British Journal of Pharmacology, Vol. 101, No. 3, 11.1990, p. 531-540.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Tolbutamide excites rat glucoreceptive ventromedial hypothallamic neurones by indirect inhibition of ATP-K+ channels

    AU - Ashford, M. L.

    AU - Boden, P. R.

    AU - Treherne, J. M.

    PY - 1990/11

    Y1 - 1990/11

    N2 - 1. The sulphonylureas, tolbutamide (0.1-10 mM) and glibenclamide (0.1-100 microM) shown not to inhibit ATP-K+ channel currents when applied to inside-out membrane patches excised from rat cultured cerebral cortex or freshly-dispersed ventromedial hypothalamic nucleus (VMHN) neurones. 2. Saturable binding sites for [3H]-glibenclamide, with similar affinity constants are present in rat cerebral cortex and hypothalamic membranes. The density of binding sites was lower in the hypothalamus than cortex. 3. Intracellular recordings from glucoreceptive VMHN neurones in hypothalamic slices were obtained. In the absence of glucose, tolbutamide (0.1 mM) depolarized these cells, increased membrane resistance and elicited action potentials. 4. Tolbutamide (0.1 mM) inhibited ATP-K+ channel currents and induced action current activity in cell-attached recordings from glucoreceptive VMHN neurones. 5. Glibenclamide (10-500 nM) had no effect per se on glucoreceptive VMHN neurones but did antagonize the actions of tolbutamide. 6. It is concluded that the hypothalamic (and perhaps cortical) sulphonylurea receptors are not directly coupled to ATP-K+ channels.

    AB - 1. The sulphonylureas, tolbutamide (0.1-10 mM) and glibenclamide (0.1-100 microM) shown not to inhibit ATP-K+ channel currents when applied to inside-out membrane patches excised from rat cultured cerebral cortex or freshly-dispersed ventromedial hypothalamic nucleus (VMHN) neurones. 2. Saturable binding sites for [3H]-glibenclamide, with similar affinity constants are present in rat cerebral cortex and hypothalamic membranes. The density of binding sites was lower in the hypothalamus than cortex. 3. Intracellular recordings from glucoreceptive VMHN neurones in hypothalamic slices were obtained. In the absence of glucose, tolbutamide (0.1 mM) depolarized these cells, increased membrane resistance and elicited action potentials. 4. Tolbutamide (0.1 mM) inhibited ATP-K+ channel currents and induced action current activity in cell-attached recordings from glucoreceptive VMHN neurones. 5. Glibenclamide (10-500 nM) had no effect per se on glucoreceptive VMHN neurones but did antagonize the actions of tolbutamide. 6. It is concluded that the hypothalamic (and perhaps cortical) sulphonylurea receptors are not directly coupled to ATP-K+ channels.

    KW - Rats, Inbred Strains

    KW - Rats

    KW - Glyburide

    KW - Cerebral Cortex

    KW - Animals

    KW - Ventromedial Hypothalamic Nucleus

    KW - Action Potentials

    KW - Tolbutamide

    KW - Adenosine Triphosphate

    KW - Potassium Channels

    KW - Male

    KW - Binding Sites

    M3 - Article

    VL - 101

    SP - 531

    EP - 540

    JO - British Journal of Pharmacology

    JF - British Journal of Pharmacology

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    ER -