van Rhee A M, van der Heijden M P, Beukers M W, IJzerman A P, Soudijn W, Nickel P
Center for Bio-Pharmaceutical Sciences, Division of Medicinal Chemistry, Leiden, The Netherlands.
Eur J Pharmacol. 1994 Jun 15;268(1):1-7. doi: 10.1016/0922-4106(94)90114-7.
Binding of the radioligand [35S]adenosine 5'-O-(2-thiodiphosphate) (ADP beta 35S) to P2 gamma purinoceptors on turkey erythrocyte membranes was used to determine the affinity of suramin and various suramin congeners belonging to different structure classes (large urea, small urea, dibenzamides and benzamides) for these receptors. Suramin was shown to be a competitive antagonist with a Ki value of 7.3 +/- 2.2 microM. The simple benzamide compound XAMR0721 (8-(3,5-dinitrophenylene carbonylimino)-1,3,5-naphthalene trisulfonate, trisodium salt) displays a high affinity for the P2 gamma purinoceptor (Ki value of 19 +/- 6 microM). Similar to suramin, compound XAMR0721 is a competitive antagonist at P2 gamma purinoceptors. In contrast to suramin, which is a potent inhibitor of the ecto-nucleotidase activity in human blood cells (44 +/- 2% residual activity at 100 microM), compound XAMR0721 is hardly active in this assay (93 +/- 1% residual activity at 100 microM). So XAMR0721, the first competitive antagonist for P2 purinoceptors that is able to discriminate between P2 purinoceptor affinity and ecto-nucleotidase activity, is an interesting pharmacological tool for the characterization of P2 purinoceptor mediated effects.
利用放射性配体[35S]腺苷5'-O-(2-硫代二磷酸)(ADPβ35S)与火鸡红细胞膜上的P2γ嘌呤受体的结合，来确定苏拉明和属于不同结构类别的各种苏拉明类似物(大尿素、小尿素、二苯甲酰胺和苯甲酰胺)对这些受体的亲和力。结果表明，苏拉明是一种竞争性拮抗剂，Ki值为7.3±2.2微摩尔。简单的苯甲酰胺化合物XAMR0721(8-(3,5-二硝基苯基亚氨基)-1,3,5-萘三磺酸钠盐)对P2γ嘌呤受体具有高亲和力(Ki值为19±6微摩尔)。与苏拉明类似，化合物XAMR0721是P2γ嘌呤受体的竞争性拮抗剂。与苏拉明不同，苏拉明是人类血细胞中外核苷酸酶活性的有效抑制剂(在100微摩尔时残留活性为44±2%)，而化合物XAMR0721在该测定中几乎没有活性(在100微摩尔时残留活性为93±1%)。因此，XAMR0721作为第一个能够区分P2嘌呤受体亲和力和外核苷酸酶活性的P2嘌呤受体竞争性拮抗剂，是表征P2嘌呤受体介导效应的一种有趣的药理学工具。
