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目的:采用竞争结合和动力学试验,研究埃他卡林对心室膜犤3H犦格列本脲(犤3H犦Glibenclamide,犤3H犦Gli)特异性结合位点的影响。方法:以吡那地尔作阳性对照,制备大鼠心室膜标本,采用竞争结合和动力学试验,研究埃他卡林对心室膜犤3H犦Gli结合特性的调节作用。结果:犤3H犦Gli与心室膜标本呈特异性、可逆性结合,非标格列本脲可剂量依赖性的取代犤3H犦Gli与心室膜标本的结合,半数抑制量值为(195±62)nmol/L。在相同条件下,埃他卡林(1nmol/L～1mmol/L)和吡那地尔(10μmol/L～1mmol/L)不取代心室膜犤3H犦Gli的特异性结合。动力学试验表明:犤3H犦Gli与心室膜标本的结合和解离均符合一级动力学。埃他卡林和吡那地尔(0.1mmol/L)虽不影响犤3H犦Gli与心室膜结合的结合动力学过程,但可加速其解离动力学过程。结论:埃他卡林与吡那地尔相似,其药理学结合位点不同于Gli结合位点,但对心室膜犤3H犦Gli特异性结合位点具有负性变构调节作用。
OBJECTIVE: To study the effect of iptakalim on the specific binding sites of 3H-glyburide (犤 3H-Glibenclamide, 犦 3H-Gli) in ventricular membranes by competitive binding assay and kinetic test. Methods: Rat ventricular membrane was prepared with pinacidil as a positive control. The binding of iptakalim to the binding characteristic of 3HL Gli in the ventricular membrane was studied by competitive binding assay and kinetic test. Results: 犤 3H 犦 Gli and ventricular membrane specimens were specific and reversible combination of non-standard glibenclamide dose-dependent replacement of 犤 3H 犦 Gli and ventricular membrane binding, half the inhibitory value of (195 ± 62 ) nmol / L. Under the same conditions, the specific binding of iptakalim (1 nmol / L ~ 1 mmol / L) and pinacidil (10 μmol / L ~ 1 mmol / L) did not replace the 3H 犦 Gli of the ventricular membrane. Kinetic experiments show: 犤 3H 犦 Gli and ventricular membrane binding and dissociation are in line with the first-order kinetics. Although the combination of iptakalim and pinacidil (0.1 mmol / L) does not affect the binding kinetics of 犤 3H 犦 Gli to the ventricular membrane, it accelerates its dissociation kinetics. CONCLUSIONS: Etatatin is similar to pinacidil and has a pharmacological binding site that is different from the Gli binding site but has a negative allosteric effect on the 3H 犦 Gli-specific binding site on the ventricular membrane.