BINDING OF THE A1-SELECTIVE ADENOSINE ANTAGONIST 8-CYCLOPENTYL-1,3-DIPROPYLXANTHINE TO RAT-BRAIN MEMBRANES
BINDING OF THE A1-SELECTIVE ADENOSINE ANTAGONIST 8-CYCLOPENTYL-1,3-DIPROPYLXANTHINE TO RAT-BRAIN MEMBRANES
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DOI：
10.1007/bf00165037
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发表时间：
1987-01-01
影响因子：
3.6
通讯作者：
HUANG, CC
中科院分区：
文献类型：
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作者：
BRUNS, RF;FERGUS, JH;HUANG, CC
8-环戊基-1,3-二丙基黄嘌呤 (PD 116,948) 是一种非常有效的 A1 选择性腺苷拮抗剂，与大鼠全脑膜中的 A1 受体结合的 3H-CHA 的 Ki 为 0.46 nM，与大鼠纹状体膜中的 A2 受体结合的 3H-NECA 的 Ki 为 340 nM。其 740 倍的 A1 选择性是腺苷拮抗剂中报道最高的。通过还原二烯丙基类似物制备 3H-PD 116,948 (117 Ci/mmol)。 3H-PD 116.948 与大鼠全脑膜的单个位点结合，Bmax 为 46 pmol/g 湿重，Kd 为 0.42 nM。非特异性结合极低，在标准条件下约占总结合的 3%，而在使用较高组织浓度时则低于 1%。抑制 3H-PD 116,948 结合的化合物的亲和力与 A1 腺苷受体高度一致。拮抗剂在 3H-PD 116,948 结合和 3H-CHA 结合方面具有同等效力，而激动剂在 3H-CHA 结合方面始终有效约 12 倍。拮抗剂的 Hill 系数为 1.0，激动剂的 Hill 系数约为 0.65。 3H-PD 116,948 应该是腺苷 A1 受体的有用拮抗剂配体。
8-Cyclopentyl-1,3-dipropylaxanthine (PD 116,948) is a very potent, very A1-selective adenosine antagonist, with a Ki of 0.46 nM in 3H-CHA binding to A1 receptors in rat whole brain membranes and 340 nM in 3H-NECA binding to A2 receptors in rat striatal membranes. Its 740-fold A1-selectivity is the highest reported for an adenosine antagonist. 3H-PD 116,948 (117 Ci/mmol) was prepared by reduction of the diallyl analog. 3H-PD 116.948 bound to a single site in rat whole brain membranes, with a Bmax of 46 pmol/g wet weight and Kd of 0.42 nM. Nonspecific binding was extremely low, amounting to about 3% of total binding under standard conditions and less than 1% when higher tissue concentrations were used. Affinities of compounds for inhibition of 3H-PD 116,948 binding were highly consistent with an A1 adenosine receptor. Antagonists were equally potent in 3H-PD 116,948 binding and in 3H-CHA binding, while agonists were consistently about 12-fold more potent in 3H-CHA binding. Hill coefficients were 1.0 for antagonists and about 0.65 for agonists. 3H-PD 116,948 should be a useful antagonist ligand for adenosine A1 receptors.