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M Fosset

Publications and source records attributed to M Fosset.

At least 37 records · Page 2Linked to original sources
PubMed1990

K+ channel openers activate brain sulfonylurea-sensitive K+ channels and block neurosecretion.

Vascular K+ channel openers such as cromakalim, nicorandil, and pinacidil potently stimulate 86Rb+ efflux from slices of substantia nigra. This 86Rb+ efflux is blocked by antidiabetic sulfonylureas, which are known to be potent and specific blockers of ATP-regulated K+ channels in pancreatic beta cells, cardiac cells, and smooth muscle cells. K0.5, the half-maximal effect of the enantiomer (-)-cromakalim, is as low as 10 nM, whereas K0.5 for nicorandil is 100 nM. These two compounds appear to have a much higher affinity for nerve cells than for smooth muscle cells. Openers of sulfonylurea-sensitive K+ channels lead to inhibition of gamma-aminobutyric acid release. There is an excellent relationship between potency to activate 86Rb+ efflux and potency to inhibit neurotransmitter release.

Animals↗
PubMed1989

Antidiabetic sulfonylureas: localization of binding sites in the brain and effects on the hyperpolarization induced by anoxia in hippocampal slices.

The distribution of antidiabetic sulfonylurea [( 3H]glibenclamide) binding sites is heterogeneous in rat brain. Pyramidal and extrapyramidal motor system contain the highest densities of sites, particularly in the substantia nigra and in the globus pallidus. Only low levels are present in the hypothalamic nuclei and the main medulla oblongata regions. In hippocampal formation the stratum lucidum and the stratum lacunosum moleculare of CA3 show an important density of glibenclamide binding sites. Electrophysiological studies with hippocampal slices show that glibenclamide blocks hyperpolarization induced by anoxia, suggesting the involvement of adenosine triphosphate-sensitive K+ channel in this early hyperpolarization event.

Action Potentials↗
PubMed1989

Regulation of ATP-sensitive K+ channels in insulinoma cells: activation by somatostatin and protein kinase C and the role of cAMP.

The actions of somatostatin and of the phorbol ester 4 beta-phorbol 12-myristate 13-acetate (PMA) were studied in rat insulinoma (RINm5F) cells by electrophysiological and 86Rb+ flux techniques. Both PMA and somatostatin hyperpolarize insulinoma cells by activating ATP-sensitive K+ channels. The presence of intracellular GTP is required for the somatostatin effects. PMA- and somatostatin-induced hyperpolarization and channel activity are inhibited by the sulfonylurea glibenclamide. Glibenclamide-sensitive 86Rb+ efflux from insulinoma cells is stimulated by somatostatin in a dose-dependent manner (half maximal effect at 0.7 nM) and abolished by pertussis toxin pretreatment. Mutual roles of a GTP-binding protein, of protein kinase C, and of cAMP in the regulation of ATP-sensitive K+ channels are discussed.

Adenoma, Islet Cell↗
PubMed1989

Molecular properties of potassium channels.

The paper describes the molecular pharmacology and biochemistry of three types of K+ channels, the calcium-activated potassium channels, ATP-regulated potassium channels and voltage-sensitive potassium channels.

Adenosine Triphosphate↗
PubMed1988

Somatostatin activates glibenclamide-sensitive and ATP-regulated K+ channels in insulinoma cells via a G-protein.

Somatostatin, an hyperglycemia-inducing hormone, was studied in rat insulinoma (RINm5F) cells using 86Rb+ efflux techniques. 86Rb+ efflux is stimulated by somatostatin in a dose-dependent manner. The half-maximum value of activation is 0.7 nM. Somatostatin-induced 86Rb+ efflux is abolished by the hypoglycemia-inducing sulfonylurea, glibenclamide, a known blocker of ATP-regulated K+ channels. Somatostatin activation is prevented by pretreatment of insulinoma cells with pertussis toxin. 86Rb+ efflux studies show that somatostatin activates an ATP-dependent K+ channel.

Adenosine Triphosphate↗
PubMed1988

Antidiabetic sulfonylureas control action potential properties in heart cells via high affinity receptors that are linked to ATP-dependent K+ channels.

Both avian and mammalian heart cells have high affinity receptors for antidiabetic sulfonylureas. The biochemical identification of these receptors has been carried out with [3H]glibenclamide. The Kd values for the most potent sulfonylureas, such as glibenclamide itself, are in the nanomolar range. Comparative studies of structure-function relationships indicate high similarities of binding properties between the sulfonylurea receptors in cardiac cells and insulinoma cells, respectively. The duration of the action potential of guinea pig cardiac cells was drastically reduced by decreasing intracellular ATP concentrations by perfusion or by blockade of oxidative phosphorylation. Glibenclamide was found to restore normal or nearly normal action potential properties in [ATP]in-depleted cardiac cells. Single channel recording using the patch-clamp technique has shown that this effect is associated with high affinity blockade of ATP-sensitive K+ channels by sulfonylureas.

ATP-Binding Cassette Transporters↗
PubMed1988

Characterization, purification, and affinity labeling of the brain [3H]glibenclamide-binding protein, a putative neuronal ATP-regulated K+ channel.

Sulfonylurea and particularly glibenclamide are potent blockers of ATP-regulated K+ channels in insulin-secreting cells. A very good correlation exists between binding of sulfonylurea to brain and insulinoma cell membranes. The [3H]glibenclamide-binding component from pig brain microsomes was solubilized with digitonin with a complete retention of its properties of interaction with glibenclamide and other sulfonylureas. A four-step purification was achieved that used (i) hydroxylapatite chromatography, (ii and iii) affinity chromatographies on ADP-agarose and wheat germ agglutinin-agarose columns, and (iv) a final chromatographic step on a mixture of AMP-agarose/GMP-agarose/hydroxylapatite. This procedure led to a 2500-fold purification. NaDodSO4/polyacrylamide gel electrophoresis of the purified material in reducing and nonreducing conditions showed that the sulfonylurea-binding component is made of a single major polypeptide chain of Mr 150,000 +/- 10,000. Direct photoaffinity labeling of the receptor with [3H]glibenclamide at different steps of the purification also showed that radioactivity was specifically incorporated into a polypeptide of Mr 150,000 +/- 5000, thus confirming the subunit structure indicated by the purification.

Adenosine Triphosphate↗
PubMed1988

ATP-sensitive K+ channels that are blocked by hypoglycemia-inducing sulfonylureas in insulin-secreting cells are activated by galanin, a hyperglycemia-inducing hormone.

The action of the hyperglycemia-inducing hormone galanin, a 29-amino acid peptide named from its N-terminal glycine and C-terminal amidated alanine, was studied in rat insulinoma (RINm5F) cells using electrophysiological and 86Rb+ flux techniques. Galanin hyperpolarizes and reduces spontaneous electrical activity by activating a population of ATP-sensitive K+ channels with a single-channel conductance of 30 pS (at -60 mV). Galanin-induced hyperpolarization and reduction of spike activity are reversed by the hypoglycemia-inducing sulfonylurea glibenclamide. Glibenclamide blocks the galanin-activated ATP-sensitive K+ channel. 86Rb+ efflux from insulinoma cells is stimulated by galanin in a dose-dependent manner. The half-maximum value of activation is found at 1.6 nM. Galanin-induced 86Rb+ efflux is abolished by glibenclamide. The half-maximum value of inhibition is found at 0.3 nM, which is close to the half-maximum value of inhibition of the ATP-dependent K+ channel reported earlier. 86Rb+ efflux studies confirm the electrophysiological demonstration that galanin activates an ATP-dependent K+ channel.

Action Potentials↗
PubMed1987

The receptor for antidiabetic sulfonylureas controls the activity of the ATP-modulated K+ channel in insulin-secreting cells.

Sulfonylureas are powerful hypoglycemic drugs that have been used for decades to treat diabetic patients. This paper describes a 86Rb+ flux technique that permits one to study easily the properties of ATP-modulated K+ channels in RINm5F insulinoma cells. Sulfonylureas inhibit this type of K+ channel under conditions of intracellular ATP depletion. The most potent sulfonylureas (glibenclamide, glipizide, and gliquidone) are acting in the nanomolar range of concentration. Inhibition of the single ATP-modulated K+ channels by low concentrations of sulfonylureas was also observed using the patch-clamp technique. The sulfonylurea receptor has been biochemically identified with [3H]glibenclamide. For 10 different sulfonylureas (or sulfonylurea analogs) there was an excellent correlation between efficacy of blockade of ATP-modulated K+ channels and efficacy of binding to the sulfonylurea receptors using the 3H-ligand.

Adenoma, Islet Cell↗
PubMed1987

Receptors for diphenylbutylpiperidine neuroleptics in brain, cardiac, and smooth muscle membranes. Relationship with receptors for 1,4-dihydropyridines and phenylalkylamines and with Ca2+ channel blockade.

Neuroleptic molecules of the diphenylbutylpiperidine series (DPBP), such as fluspirilene, penfluridol, pimozide and clopimozide, antagonize binding of (-)[3H]desmethoxyverapamil ((-)[3H]D888) and (+)[3H]PN 200-110 to rabbit brain, heart and smooth muscle membranes. The diphenylbutylpiperidine binding site in all these tissues is distinct but is allosterically related to the 1,4-dihydropyridine binding site and to the phenylalkylamine binding site. High and low affinity binding sites for (-)D888 were identified. (-)[3H]D888 binding at both types of sites was inhibited following the saturation of a single type of diphenylbutylpiperidine binding site. Half-maximal inhibition (K0.5) of brain, heart and smooth muscle membranes binding by different diphenylbutylpiperidines was in the range of 10-100 nM. These K0.5 values were one to two orders of magnitude higher than those found for the high affinity diphenylbutylpiperidine receptor in skeletal muscle membranes. The K0.5 values found in binding experiments in smooth muscle were similar to the (IC50) values for half-maximal inhibition by diphenylbutylpiperidine of voltage-dependent 45Ca2+ influx through the slow Ca2+ channel.

Animals↗
PubMed1987

Identification in mammalian brain of an endogenous substance with Na+ channel blocking activities similar to those of tetrodotoxin.

A substance with Na+ channel blocking activities has been isolated from pig brain after extraction and purification on sulfopropyl-Sephadex C-25, reversed-phase and carboxymethyl Synchropak high pressure liquid chromatography columns. The peptidic material i) displaces [3H]ethylenediamine tetrodotoxin ([3H]en-TTX) from its binding sites on rat brain membranes, (ii) it blocks 22Na+ influx induced by veratridine and sea anemone toxin on neuroblastoma and embryonic chick heart cells in culture, (iii) it specifically decreases the height of the action potential generated in frog sciatic nerve, and (iv) it blocks the fast Na+ current in voltage-clamped neuroblastoma cells. These properties are similar to those of tetrodotoxin while the endogenous factor is a peptide that is destroyed by proteases. These results suggest the presence in pig brain of a potent Na+ channel modulation activity.

Action Potentials↗
PubMed1987

The antidiabetic sulfonylurea glibenclamide is a potent blocker of the ATP-modulated K+ channel in insulin secreting cells.

The ATP-sensitive K+ channel of RINm5F insulinoma cells is activated after an intracellular ATP depletion. This activation can be followed by 86Rb+ efflux. Once activated by ATP depletion, the K+ channel can be blocked by the hypoglycemic drug, glibenclamide. The blockade is of a high-affinity type (K0.5 = 0.06 nM). Recording of the activity of ATP-sensitive K+ channels with the patch-clamp technique confirmed that they could be completely blocked with 20 nM glibenclamide.

Adenosine Triphosphate↗