Hall D A, Hourani S M
Receptors and Cellular Regulation Research Group, School of Biological Sciences, University of Surrey, Guildford, U.K.
Biochem Pharmacol. 1994 Mar 15;47(6):1013-8. doi: 10.1016/0006-2952(94)90412-x.
The effects of the P2-purinoceptor antagonist, suramin, on ADP-induced increases in human platelet cytosolic calcium concentration ([Ca2+]i) and inhibition of prostaglandin E1 (PGE1)-stimulated adenylate cyclase activity were investigated. Suramin (50-200 microM) acted as an antagonist of ADP-induced increases in [Ca2+]i, causing parallel, rightward shifts of the log concentration-response curve to ADP with no apparent depression of the maximal response. However, the slope of the Schild plot was 2.3 +/- 0.3, similar to that obtained in previous studies on aggregation, indicating that the antagonism was not simply competitive. The apparent pA2 for suramin, taken from the Schild plot, was 4.63, similar to that for suramin's inhibition of aggregation, which suggests that these two effects are closely related. Suramin was not specific for the ADP receptor, however, as it was also able to inhibit, non-competitively, increases in [Ca2+]i induced by 5-hydroxytryptamine. Suramin (50-400 microM) also inhibited the effect of ADP on PGE1-stimulated accumulation of cyclic AMP, causing parallel shifts of the log concentration-response curve to ADP, with a Schild plot slope of 1.00 +/- 0.10, suggesting competitive antagonism, and a pA2 value of 5.09. Suramin (400 microM) did not reduce the inhibition of cyclic AMP accumulation by adrenaline, although it was able to inhibit the accumulation of cyclic AMP caused by PGE1, again showing that suramin has some non-specific effects. These data suggest that suramin is an antagonist at the platelet ADP receptor mediating increases in [Ca2+]i and inhibition of adenylate cyclase, but that it also shows non-specific effects and can depress platelet responses to other agonists. In addition, the similar pA2 value of suramin for the two effects of ADP does not support suggestion that they are mediated by two different receptors on human platelets.
研究了P2嘌呤受体拮抗剂苏拉明对ADP诱导的人血小板胞浆钙浓度（[Ca2+]i）升高以及对前列腺素E1（PGE1）刺激的腺苷酸环化酶活性的抑制作用。苏拉明（50 - 200微摩尔）作为ADP诱导的[Ca2+]i升高的拮抗剂，使对数浓度 - 反应曲线向ADP平行右移，最大反应无明显降低。然而，Schild图的斜率为2.3±0.3，与先前关于聚集的研究结果相似，表明这种拮抗作用并非简单的竞争性。从Schild图得出的苏拉明的表观pA2为4.63，与苏拉明对聚集的抑制作用相似，这表明这两种效应密切相关。然而，苏拉明对ADP受体并不具有特异性，因为它也能够非竞争性地抑制5 - 羟色胺诱导的[Ca2+]i升高。苏拉明（50 - 400微摩尔）还抑制了ADP对PGE1刺激的环磷酸腺苷（cAMP）积累的作用，使对数浓度 - 反应曲线向ADP平行移动，Schild图斜率为1.00±0.10，提示竞争性拮抗作用，pA2值为5.09。苏拉明（400微摩尔）虽然能够抑制PGE1引起的cAMP积累，但并未降低肾上腺素对cAMP积累的抑制作用，再次表明苏拉明具有一些非特异性作用。这些数据表明，苏拉明是介导[Ca2+]i升高和腺苷酸环化酶抑制的血小板ADP受体拮抗剂，但它也表现出非特异性作用，并能抑制血小板对其他激动剂的反应。此外，苏拉明对ADP两种效应的相似pA2值不支持它们由人血小板上两种不同受体介导的观点。
