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Tolbutamide excites rat glucoreceptive ventromedial hypothallamic neurones by indirect inhibition of ATP‐K + channels
Author(s) -
Ashford M.L.J.,
Boden P.R.,
Treherne J.M.
Publication year - 1990
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.1476-5381.1990.tb14116.x
Subject(s) - tolbutamide , glibenclamide , endocrinology , medicine , hypothalamus , chemistry , intracellular , biophysics , cerebral cortex , receptor , channel blocker , membrane potential , tetraethylammonium , ventromedial nucleus of the hypothalamus , biology , biochemistry , calcium , insulin , potassium , diabetes mellitus , organic chemistry
1 The sulphonylureas, tolbutamide (0.1–10 m m ) and glibenclamide (0.1–100 μ m ) were 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 hypothalmic nucleus (VMHN) neurones. 2 Saturable binding sites for [ 3 H]‐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 m m ) depolarized these cells, increased membrane resistance and elicited action potentials. 4 Tolbutamide (0.1 m m ) inhibited ATP‐K + channel currents and induced action current activity in cell‐attached recordings from glucoreceptive VMHN neurones. 5 Glibenclamide (10–500 n m ) 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.