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Adenine nucleotide‐induced inhibition of binding of sulphonylureas to their receptor in pancreatic islets
Author(s) -
Schwanstecher M.,
Löser S.,
Brandt Ch.,
Scheffer K.,
Rosenberger F.,
Panten U.
Publication year - 1992
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.1476-5381.1992.tb09014.x
Subject(s) - glibenclamide , tolbutamide , chemistry , pancreatic islets , adenosine triphosphate , dissociation constant , adenosine , nucleotide , medicine , binding site , endocrinology , diazoxide , phosphorylation , receptor , biochemistry , insulin , islet , biology , diabetes mellitus , gene
1 The effects of the Mg complex of adenosine 5′‐triphosphate (MgATP) on binding of sulphonylureas to microsomes obtained from mouse pancreatic islets were examined. 2 MgATP inhibited the binding of both glibenclamide and tolbutamide to microsomes. 3 Binding of [ 3 H]‐glibenclamide inhibited by MgATP was not further diminished by Mg 2+ ‐bound adenosine 5′‐(β,γ‐imidotriphosphate) (AMP‐PNP) or free adenosine 5′‐diphosphate (ADP). Higher concentrations of MgAMP‐PNP induced a partial reversal of the inhibitory effect of MgATP on [ 3 H]‐glibenclamide binding. 4 The apparent dissociation constant ( K ' D ) for binding of [ 3 H]‐glibenclamide remained constant when the MgATP concentration was increased from 100 to 500 μ m . 5 Extracellular ADP did not markedly stimulate insulin release from mouse pancreatic islets. 6 It is concluded that sulphonylureas and cytosolic nucleotides exert their inhibitory effects on the K‐ATP‐channels of β‐cells by binding to different sites. The binding properties of the sulphonylurea receptor seem to be modulated by protein phosphorylation.