2 BINDING-SITES FOR [H-3] GLIBENCLAMIDE IN THE RAT-BRAIN

The binding of [H-3]glibenclamide, a potent sulfonylurea which blocks ATP-sensitive potassium channels, was studied in the rat brain. A Scatchard plot of saturation isotherms suggests that [H-3]glibenclamide binds in various brain regions to a high- and a low-affinity binding site (K(d) values of 0.21 nM and 111 nM and B(max) values of 41 and 1060 fmol/mg protein, respectively). Competitive binding assays with various unlabelled sulfonylureas showed biphasic displacements of [H-3]glibenclamide with pseudo-Hill coefficients significantly different from unity. These data indicate the existence of a heterogeneity of binding sites to [H-3]glibenclamide in the rat brain; this may correlate with the variability of effects of sulfonylureas observed from physiological experiments.