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Specificity of Nonadrenergic Imidazoline Binding Sites in Insulin‐Secreting Cells and Relation to the Block of ATP‐Sensitive K 1 Channels
Author(s) -
GROSSELACKMANN TIMM,
ZÜNKLER BERND J.,
RUSTENBECK INGO
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1304.050
Subject(s) - imidazoline receptor , clonidine , chemistry , protein subunit , binding site , insulin , quinine , pharmacology , biophysics , medicine , endocrinology , stereochemistry , biochemistry , biology , malaria , immunology , gene
A bstract : To characterize the specificity of nonadrenergic imidazoline binding sites of insulin‐secreting HIT cells, competitive binding of insulinotropic imidazolines and quinine was measured and compared with the effect of these compounds on native K ATP channels and with a heterologously expressed variant of the pore‐forming subunit (Kir6.2 DC26). There were two nonadrenergic imidazoline binding sites for [ 3 H]clonidine with K d values of 61 nM and 4.5 mM, respectively. Quinine reduced specific binding incompletely (73%) with K i values of 75 nM and 133 mM. Clonidine, N‐allyl‐clonidine (alinidine), and quinine inhibited native K ATP channels as well as Kir6.2DC26 channels. Coexpression of Kir6.2DC26 and SUR1 (the regulatory subunit of K ATP ) did not increase the potency of quinine. There are nonadrenergic imidazoline binding sites in insulin‐secreting HIT cells which also recognize quinine. One of these sites is Kir6.2, the pore‐forming subunit of the K ATP channel.