Sulfonylurea affinities and potencies in recombinant and native KATP channels
| Glibenclamide | Glipizide | Meglitinide | Tolbutamide | |||||
|---|---|---|---|---|---|---|---|---|
| KD | EC50 | KD | EC50 | KD | EC50 | KD | EC50 | |
| ha SUR1/KIR6.2 | 0.72 nM (0.94) | 0.13 nM (1.23) | 17 nM (0.94) | 3.8 nM (1.26) | 6.9 μM (0.93) | 1.2 μM (1.26) | 29 μM (0.98) | 4.9 μM (1.30) |
| pancreatic β cells | 1.4 nM (0.96)a | 0.05 nM (1.51)b | 21 nM (0.96) | 4.0 nM (n.d.)c | 7.8 μM (0.97) | 0.5 μM (1.30)c | 32 μM (0.93)d | 2.5 μM (1.53)e |
| rat SUR2B/KIR6.2 | 250 nM (0.96) | 42 nM (1.27) | 6.1 μM (0.99) | 1.2 μM (1.32) | 9.2 μM (0.93) | 1.6 μM (1.26) | 260 μM (1.02) | 88 μM (1.29) |
| aortic rings (rat) | 430 nM (1.12)f | 97 nM (1.20)f | 6.3 μM (1.00)f | 1.5 μM (1.25)f | n.d. | n.d. | n.d. | n.d. |
Dissociation constants (K Ds) for hamster SUR1 or rat SUR2B and EC50 values to inhibit activity of recombinant channels were taken from Figs. 1 and 2. K Ds for binding of glipizide and meglitinide to pancreatic β cells were assessed in a membrane fraction from mouse pancreatic islets using a [3H]glibenclamide displacement assay (see Experimental Procedures). The other data are from: a Schwanstecher et al., 1991; b Gromada et al., 1995; c Zünkler et al., 1988; d Schwanstecher et al., 1992b; e Gillis et al., 1989; f Quast et al., 1993. EC50 values to inhibit β cell K ATP channel activity were measured using the cell-attached (e) or the whole-cell configuration (b, c) of the patch-clamp technique. Data for intact aortic rings were assessed using [3H]P1075 displacement and inhibition of86Rb+ efflux (f). n.d. = not determined.