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S Behrends

Publications and source records attributed to S Behrends.

At least 127 records · Page 7Linked to original sources
PubMed1992

Effect of MgATP on pinacidil-induced displacement of glibenclamide from the sulphonylurea receptor in a pancreatic beta-cell line and rat cerebral cortex.

1. The effects of blockers and openers of K+ channels on binding of [3H]-glibenclamide to microsomes obtained from a pancreatic beta-cell line (HIT-T15) or rat cerebral cortex were examined. 2. The blockers quinine, chlorpromazine and thiopentone and the openers cromakalim [(+/- ) 6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1- pyrrolidyl)-2H-benzo[b]pyran-3-ol] and minoxidil sulphate did not significantly interact with the sulphonylurea receptor of HIT-cells both at phosphorylating (presence of MgATP) and dephosphorylating (absence of MgATP) conditions. 3. In the absence of MgATP, pinacidil (200-500 microM) did not significantly displace [3H]-glibenclamide binding to microsomes from HIT-cells. The displacement of [3H]-glibenclamide binding was strongly enhanced by MgATP and was due to a decrease in the number of high affinity binding sites for glibenclamide. 4. MgATP enhanced pinacidil-induced inhibition of [3H]-glibenclamide binding to microsomes from rat cerebral cortex. 5. The effect of MgATP on pinacidil-induced inhibition of [3H]-glibenclamide binding was maintained after solubilization of the membranes from HIT-cells or rat cerebral cortex. 6. It is concluded that the sulphonylurea receptor is regulated not only by sulphonylureas but also by the K+ channel openers, diazoxide and pinacidil, and by protein phosphorylation. The binding sites for sulphonylureas and these K+ channel openers are not identical, but appear to be located at a single protein or at tightly associated proteins.

ATP-Binding Cassette Transporters↗
PubMed1992

The binding properties of the solubilized sulfonylurea receptor from a pancreatic B-cell line are modulated by the Mg(++)-complex of ATP.

Previous studies demonstrated that the Mg complex of ATP decreases glyburide- and increases diazoxide-binding to membranes from pancreatic islets. To examine further the mechanism of these effects, the sulfonylurea receptors in microsomes of the hamster B-cell line HIT-T15 were solubilized with detergents. Maximum recovery of receptors (40%) was obtained with Triton X-100. Specific binding of [3H]glyburide to the solubilized receptors (Kd = 0.35 nM, maximum number of binding sites = 170 fmol/mg of protein) corresponded well to specific binding to microsomes. In Triton X-100 extracts, MgATP (300 microM) reduced the number of high-affinity sites for [3H]glyburide by 50% and increased the dissociation constant for [3H]glyburide by 4-fold; MgATP was half-maximally effective at 20 microM. Development of MgATP-induced inhibition of [3H]glyburide binding to solubilized binding sites was not slower than dissociation of [3H]glyburide binding. Alkaline phosphatase accelerated the reversal of MgATP-induced inhibition of [3H]glyburide binding. In the presence of Mg++, not only ATP but also ADP, GTP and GDP inhibited [3H]glyburide binding to the solubilized receptor. However, MgADP did not inhibit [3H]glyburide binding when the MgATP concentration was kept low by the hexokinase reaction. MgATP significantly enhanced diazoxide-induced displacement of [3H]glyburide from the solubilized receptor. The MgATP-induced inhibition of binding was weakened by millimolar concentrations of free ATP. It is concluded that the binding sites for MgATP, glyburide and diazoxide are located at a single protein or at closely associated proteins which may include a protein kinase.

ATP-Binding Cassette Transporters↗