PPADS and suramin as antagonists at cloned P-2Y- and P-2U-purinoceptors
PPADS and suramin as antagonists at cloned P-2Y- and P-2U-purinoceptors
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DOI：
10.1111/j.1476-5381.1996.tb15457.x
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发表时间：
1996-06-01
影响因子：
7.3
通讯作者：
Boarder, MR
中科院分区：
文献类型：
--
作者：
Charlton, SJ;Brown, CA;Boarder, MR
1观察苏拉明和pyridoxalphosphate-6-azophenyl-2‘，4’-disulphonic酸(PPADS)对转P-2U受体的1321N1细胞(h-P-2U-1321N1细胞)和转火鸡P-2Y受体的1321N1细胞(t-P-2Y-1321N1细胞)对磷脂酶C刺激的影响。2苏拉明使t-P-2Y-1321N1细胞的2MeSATP量效曲线平行右移，其pA(2)值为5.77+/-0.11.3苏拉明也使h-P-2U-1321N1细胞的UTP量效曲线右移。SChild样地的坡度不同于1(1.57+/-0.19)，表观Pa值为4.32+/-0.13。4在胞外核苷酸酶抑制剂ARL 67156(6-N，N-二乙基-β，γ-二溴亚甲基-D-三磷酸腺苷)存在下，两种细胞类型的EC(50)和曲线形状没有显著差异，对苏拉明的PA(2)值也没有差异。5 PPADS使t-P-2Y-321N1细胞对2MeSATP的EC(50)增加。SChild曲线的斜率不同于单位(0.55+/-0.15)，X截距对应的表观pA(2)为5.98+/-0.65.6，PPADS高达30 mM对h-P-2U-1321N1细胞UTP的浓度-反应曲线没有影响。7综上所述，苏拉明和PPADS在两种受体类型上的作用明显不同，在P-2Y-过敏剂和P-2U-过敏剂上的拮抗作用都显著高于P-2U-过敏剂。胞外核苷酸酶的降解对这两种受体类型的反应的性质或它们对苏拉明的不同敏感性几乎没有影响。
1 The effect of suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) on the stimulation of phospholipase C in 1321N1 cells transfected with the P-2U-purinoceptor (h-P-2U-1321N1 cells) or with the turkey P-2Y-purinoceptor (t-P-2Y-1321N1 cells) was investigated. 2-methylthioadenosine triphosphate (2MeSATP) was used as the agonist at t-P-2Y-1321N1 cells and uridine triphosphate (UTP) at h-P-2U-1321N1 cells.2 Suramin caused a parallel shift to the right of the concentration-response curves for 2MeSATP in the t-P-2Y-1321N1 cells, yielding a Schild plot with a slope of 1.16+/-0.08 and a pA(2) value of 5.77+/-0.11.3 Suramin also caused a shift to the right of concentration-response curves for UTP in the h-P-2U-1321N1 cells, and on Schild plots gave a slope different from unity (1.57+/-0.19) and an apparent pA(2) value of 4.32+/-0.13. Suramin was therefore a less potent antagonist at the P-2U-purinoceptor than the P-2Y-purinoceptor.4 In the presence of the ectonucleotidase inhibitor, ARL 67156 (6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP) there was no significant difference in the EC(50) or shapes of curves with either cell type, and no difference in PA(2) values for suramin.5 PPADS caused an increase in the EC(50) for 2MeSATP in the t-P-2Y-321N1 cells. The Schild plot had a slope different from unity (0.55+/-0.15) and an X-intercept corresponding to an apparent pA(2) of 5.98+/-0.65.6 PPADS up to 30 mu M had no effect on the concentration-response curve for UTP with the h-P-2U-1321N1 cells.7 In conclusion, suramin and PPADS show clear differences in their action at the 2 receptor types, in each case being substantially more effective as an antagonist at the P-2Y-purinoceptor than at the P-2U-purinoceptor. Ectonucleotidase breakdown had little influence on the nature of the responses at the two receptor types, or in their differential sensitivity to suramin.