DIFFERENTIAL-EFFECTS OF P-2-PURINOCEPTOR ANTAGONISTS ON PHOSPHOLIPASE C-COUPLED AND ADENYLYL CYCLASE-COUPLED P-2Y-PURINOCEPTORS
DIFFERENTIAL-EFFECTS OF P-2-PURINOCEPTOR ANTAGONISTS ON PHOSPHOLIPASE C-COUPLED AND ADENYLYL CYCLASE-COUPLED P-2Y-PURINOCEPTORS
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DOI：
10.1111/j.1476-5381.1994.tb17034.x
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发表时间：
1994-10-01
影响因子：
7.3
通讯作者：
HARDEN, TK
中科院分区：
文献类型：
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作者：
BOYER, JL;ZOHN, IE;HARDEN, TK
1 刺激火鸡红细胞和许多其他细胞类型上的 P-2Y-嘌呤受体会导致磷脂酶 C 的激活。相反，我们最近观察到 C6 大鼠神经胶质瘤细胞上的 P-2Y-嘌呤受体不与磷脂酶 C 偶联，而是抑制腺苷酸环化酶。2 在本研究中，我们研究了 P-2-嘌呤受体拮抗剂、苏拉明、活性蓝的药理学选择性2、磷酸吡哆醛 6-偶氮苯基 2',4'-二磺酸 (PPADS) 用于磷脂酶 C- 和腺苷酸环化酶偶联的 P-2Y-嘌呤受体。3 在 C6 胶质瘤细胞中，苏拉明和活性蓝 2 竞争性拮抗 2MeSATP 对腺苷酸环化酶的抑制作用 (pK(B) = 5.4 +/-分别为 0.2 和 7.6 +/- 0.1），而浓度高达 100 μM 的 PPADS 则没有效果。4 相反，在火鸡红细胞制剂中，浓度高达 30 μM 的 PPADS 是 P-2Y 嘌呤受体刺激的磷脂酶 C 活性的竞争性拮抗剂（pK(B) = 5.9 +/- 0.1）。苏拉明和活性蓝 2 使 2MeSATP 激活磷脂酶 C 的浓度效应向右移动，并显着降低最大磷酸肌醇反应。5 火鸡红细胞还表达磷脂酶 C 偶联的 β-肾上腺素受体。竞争性抑制 P-2Y-嘌呤受体介导的反应的 PPADS 浓度对 β-肾上腺素受体激活磷脂酶 C 的影响很小。相反，苏拉明和活性蓝 2 产生非竞争性抑制，其特征是对异丙肾上腺素的最大反应降低，但这种 β-肾上腺素受体激动剂的效力没有变化。6 PPADS 对 C6 胶质瘤细胞和火鸡红细胞的 P-2Y-嘌呤受体的不同作用进一步支持了不同 P-2Y-嘌呤受体亚型介导与腺苷酸偶联的观点。环脂酶和磷脂酶 C.
1 Stimulation of P-2Y-purinoceptors on turkey erythrocytes and many other cell types results in activation of phospholipase C. In contrast, we have observed recently that P-2Y-purinoceptors on C6 rat glioma cells are not coupled to phospholipase C, but rather, inhibit adenylyl cyclase.2 In this study we investigated the pharmacological selectivity of the P-2-purinoceptor antagonists, suramin, reactive blue 2, and pyridoxal phosphate 6-azophenyl 2',4'-disulphonic acid (PPADS) for phospholipase C- and adenylyl cyclase-coupled P-2Y-purinoceptors.3 In C6 glioma cells, suramin and reactive blue 2 competitively antagonized the inhibitory effect of 2MeSATP on adenylyl cyclase (pK(B) = 5.4 +/- 0.2 and 7.6 +/- 0.1, respectively), whereas PPADS at concentrations up to 100 mu M had no effect.4 In contrast, in the turkey erythrocyte preparation, PPADS at concentrations up to 30 mu M was a competitive antagonist of P-2Y-purinoceptor-stimulated phospholipase C activity (pK(B) = 5.9 +/- 0.1). Suramin and reactive blue 2 produced both a shift to the right of the concentration-effect of 2MeSATP for the activation of phospholipase C and a significant decrease in the maximal inositol phosphate response.5 Turkey erythrocytes also express a phospholipase C-coupled beta-adrenoceptor. Concentrations of PPADS that competitively inhibited the P-2Y-purinoceptor-mediated response had only minimal effects on the activation of phospholipase C by beta-adrenoceptors. In contrast, suramin and reactive blue 2 produced a non-competitive inhibition, characterized by decreases in the maximal response to isoprenaline with no change in the potency of this beta-adrenoceptor agonist.6 The differential effect of PPADS on P-2Y-purinoceptors of C6 glioma cells and turkey erythrocytes adds further support to the idea that different P-2Y-purinoceptor subtypes mediate coupling to adenylyl cyclic and phospholipase C.