Ionic Effects on the Uptake of Sulfonylurea (Glibenclamide) by Pancreatic Islets

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