Evidence for the distinct nature of F2-isoprostane receptors from those of thromboxane A2.
Evidence for the distinct nature of F2-isoprostane receptors from those of thromboxane A2.
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F2-异前列腺素受体与血栓素 A2 受体不同性质的证据。
DOI：
10.1152/ajprenal.1997.272.4.f477
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Badr,KF
中科院分区：
文献类型：
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作者：
Fukunaga,M;Yura,T;Grygorczyk,R;Badr,KF
在大鼠肾小球和系膜细胞中，血栓素A2（TxA 2）模拟物U-46，619（而非8-异前列腺素F2 α（8-iso-PGF 2 α））减少了肾小球菊粉空间并增加了1，4，5-三磷酸肌醇的产生，SQ-29，548消除了该效应。在使用8-iso-[3 H] PGF 2 α或[3 H]SQ-29，548的竞争性结合研究中，系膜细胞显示TxA 2结合位点，但不显示8-iso-PGF 2 α的结合位点。相比之下，大鼠主动脉平滑肌细胞具有TxA 2和8-iso-PGF 2 α的特异性结合位点，并显示对两种激动剂的功能反应，如促分裂原活化蛋白激酶的时间和剂量依赖性激活。在这些细胞中，异前列烷受体的平均解离常数值为31.8 +/- 5.7 nM。当人TxA 2受体cDNA在注射Ca 2+特异性光蛋白、水母发光蛋白、8-iso-PGF 2 α的爪蟾卵母细胞中表达时，其反应比U-46，619弱得多。这些研究提供了F2-异前列烷受体的第一个放射性配体结合特征，并证明了其特异性和异源性细胞定位。这些研究支持异前列烷受体的独特性质和生物学意义，并为其进一步的分子表征提供了工具。
In rat glomeruli and mesangial cells, the thromboxane A2 (TxA2) mimetic, U-46,619, but not 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), reduced glomerular inulin space and increased inositol 1,4,5-trisphosphate production, effects abolished by SQ-29,548. In competitive binding studies using 8-iso-[3H]PGF2alpha or [3H]SQ-29,548, mesangial cells displayed TxA2 binding sites but not ones for 8-iso-PGF2alpha. In contrast, rat aortic smooth muscle cells possessed specific binding sites for both TxA2 and 8-iso-PGF2alpha and displayed functional responses to both agonists, such as time- and dose-dependent activation of mitogen-activated protein kinases. In these cells, the mean dissociation constant value for the isoprostane receptor was 31.8 +/- 5.7 nM. When human TxA2 receptor cDNA was expressed in Xenopus oocytes injected with the Ca2+-specific photoprotein, aequorin, 8-iso-PGF2alpha gave much weaker responses than U-46,619. These studies provide the first radioligand binding characteristics of the F2-isoprostane receptor and demonstrate its specific and heterologous cellular localization. These studies support the distinct nature and biological significance of isoprostane receptors and provide a tool for their further molecular characterization.