ATP 민감성 칼륨통로의 약물결합 특성 = Characteristics of Specific Binding of ATP - sensitive Potassium Channel Blockers in Human , Guinea Pig and Rat Cerebral Cortex Membranes

다국어 초록 (Multilingual Abstract)

We examined the compertition of [³H]glibenclamide ([³H]GBC) with several K - ATP(ATP-sensitive po-tassium channel) blockers (PCB) of different chemical structure in rat, guinea pig and human cortex me-mbranes. [³H]GBC was chosen as a probe because it possesses both benzoic acid and sulfonylurea. In both rat and guinea pig cortex, analysis of competition curves indicated a single population of [³H]GBC binding sites. There are 2 kinds of binding site in human cerbral cortex membranes, one is high affinity with smaller binding capacity, and the other is low affinity with larger binding capacity. Glipizide, another hypoglycemic agent structurally similar to GBC, sensitively, but not as much as GBC, inhibited [³H]GBC binding to rat, guinea pig and human cerebral cortex membranes with different Ki values. Meglitinide, an hypoglycemic drug derived from benzoic acid, inhibited [³H]GBC binding in preparations from all the spe-cies tested with much lower Ki values. Tolbutamide, a sulfonylurea derivative, also inhibited [³H]GBC bin-ding to cortex membranes of those species with larger Ki values than that of meglitinide. The rank of po-tency of inhibition of [³H]GBC binding is well correlated with therapeutic doses in man. These results suggest that there are species differences in characteristics of receptor binding and sulfon-ylurea and benzoic acid are needed to ensure higher receptor binding ability.
(Key words : ATP-Sensitive potassium channel, human, rat, guinea pig, brain, binding)