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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Mg(2+)-dependent inhibition of KATP by sulphonylureas in CRI-G1 insulin-secreting cells.

1 Patch-clamp recording techniques were used to examine the effects of tolbutamide, glibenclamide, meglitinide and thiopentone on KATP in CRI-GI insulin-secreting cells in the presence and absence of Mg2+. 2 In the absence of Mg2+ in the intracellular bathing solution, tolbutamide was significantly less effective when applied either to the intracellular or to the extracellular surfaces of cell-free patches. Removal of extracellular Mg2+ did not alter the effectiveness of tolbutamide provided that Mg2+ was present at the intracellular surface of the patch. 3 Tolbutamide was also significantly less effective when applied to the intracellular surface of cell-free patches when Mn2+ was used as a replacement for Mg2+. 4 Both the sulphonylurea, glibenclamide and the non-sulphonylurea derivative, meglitinide also showed Mg2+ dependent inhibitory effects in cell-free patches. In contrast, the barbiturate thiopentone inhibited KATP in a Mg(2+)-independent manner. 5 Whole-cell IK(ATP) were used to quantify the effects of tolbutamide and glibenclamide in the presence and absence of intracellular Mg2+. Concentration-inhibition curves, in the presence of intracellular Mg2+, resulted in IC50 values of 12.1 microM and 2.1 nM for tolbutamide and glibenclamide, respectively. In the absence of intracellular Mg2+, the corresponding IC50 values were 25.3 mM and 3.6 microM, respectively. The values of IC50 for thiopentone in the presence and absence of intracellular Mg2+ were 69.4 microM and 69.2 microM, respectively. 6 With respect to the high affinity binding sites for [3H]-glibenclamide in CRI-G1 membranes, no significant differences were found between the dissociation constants for, or the maximal binding capacities of, [3H]-glibenclamide in the presence or absence of Mg2+.(ABSTRACT TRUNCATED AT 250 WORDS)[1]

References

  1. Mg(2+)-dependent inhibition of KATP by sulphonylureas in CRI-G1 insulin-secreting cells. Lee, K., Ozanne, S.E., Hales, C.N., Ashford, M.L. Br. J. Pharmacol. (1994) [Pubmed]
 
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