Abstract
The accumulation of glibenclamide was studied in the pancreatic islets of non-inbred
ob/ob-mice. Microdissected islets were incubated in media of different ionic composition
and the accumulation measured as the uptake of drug not accounted for by equilibration
in the urea space. In 12 mM N-hydroxyethylpiperazine-N'-2-ethane sulphonic acid (HEPES)
buffer the accumulation was only half of that in Krebs-Ringer bicarbonate buffer.
Addition of 50 mM NaCl, Na2SO4, KCl, or LiCl to the HEPES buffer restored the accumulation to the level seen in
Krebs-Ringer buffer. Studies with different concentrations of NaCl and Na2SO4 showed that the glibenclamide accumulation was sensitive to Na+ with little or no effect being attributable to the anions. CaCl2 or MgCl2 had much stronger effects than NaCl. It is concluded that cations participate in
the binding of glibenclamide to β-cells. The mechanism could be an increased ionic
attraction between cell surfaces and hydrophilic regions of the drug, or a shielding
of fixed surface anions allowing stronger hydrophobic interactions between drug and
β-cells.
Key words
Cations - Pancreatic Islets - Glibenclamide Binding
