Klapperstück M, Büttner C, Nickel P, Schmalzing G, Lambrecht G, Markwardt F
Julius-Bernstein-Institute for Physiology, Martin-Luther-University Halle, Magdeburger Strasse 6, D-06097, Halle, Germany.
Eur J Pharmacol. 2000 Jan 17;387(3):245-52. doi: 10.1016/s0014-2999(99)00826-2.
The effect of the suramin analogue 8,8'-(carbonylbis(imino-4, 1-phenylenecarbonylimino-4,1-phenylenecarbonylimino))bis(1,3 , 5-naphthalenetrisulfonic acid) (NF279) was analyzed on human P2X(1) and P2X(7) receptor subtypes (human P2X(1) and human P2X(7)) heterologously expressed in Xenopus oocytes using the two-microelectrode voltage-clamp technique. At activating ATP concentrations of 1 microM (human P2X(1)) and 10 microM ATP (human P2X(7)), IC(50) values of 0.05 microM and 2.8 microM were found for human P2X(1) and human P2X(7) receptors, respectively. An increase in the activating [ATP] shifted the NF279 concentration-inhibition curve rightwards for both receptors. NF279 slowed the activation of both human P2X(1) and human P2X(7) as well as the desensitization of human P2X(1). The data support a model in which desensitization of P2X(1) is dependent on preceding activation of these P2X receptors. It is concluded that NF279 acts as a competitive antagonist with much higher potency at human P2X(1) than at P2X(7) receptors. NF279 may hence be suited to discriminate between both receptors in native tissues.
使用双微电极电压钳技术，分析了苏拉明类似物8,8'-（羰基双（亚氨基-4,1-亚苯基羰基亚氨基-4,1-亚苯基羰基亚氨基））双（1,3,5-萘三磺酸）（NF279）对非洲爪蟾卵母细胞中异源表达的人P2X(1)和P2X(7)受体亚型（人P2X(1)和人P2X(7)）的作用。在1 μM（人P2X(1)）和10 μM ATP（人P2X(7)）的激活ATP浓度下，人P2X(1)和人P2X(7)受体的IC(50)值分别为0.05 μM和2.8 μM。激活[ATP]的增加使两种受体的NF279浓度抑制曲线向右移动。NF279减缓了人P2X(1)和人P2X(7)的激活以及人P2X(1)的脱敏。数据支持一种模型，其中P2X(1)的脱敏依赖于这些P2X受体的先前激活。结论是，NF279作为一种竞争性拮抗剂，对人P2X(1)的效力远高于对P2X(7)受体的效力。因此，NF279可能适用于区分天然组织中的两种受体。
