[3H]AF-DX 116 labels subsets of muscarinic cholinergic receptors in rat brain and heart.
[3H]AF-DX 116 labels subsets of muscarinic cholinergic receptors in rat brain and heart.
复制标题
[3H]AF-DX 116 标记大鼠大脑和心脏中的毒蕈碱胆碱能受体亚群。
DOI：
10.1016/0024-3205(87)90604-7
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发表时间：
1987
期刊：
影响因子：
6.1
通讯作者：
Yamamura,HI
中科院分区：
文献类型：
--
作者：
Wang,JX;Roeske,WR;Gulya,K;Wang,W;Yamamura,HI
The in vitro binding properties of the novel muscarinic antagonist [3 H] AF-DX 116 were studied using a rapid filtration technique. Association and dissociation rates of [3 H] AF-DX 116 binding were rapid at 25° C (2.74 and 2.70× 10 7 min− 1 M− 1 for k+ 1; 0.87 and 0.93 min− 1 for k− 1) but 20–40 times slower at 0–4° C (0.13 and 0.096× 10 7 min− 1 M− 1 for k+ 1; 0.031 and 0.022 min− 1 for k− 1 in cerebral cortical and cardiac membranes, respectively). Kinetic dissociation constants (K d s) were estimated to be 31.8 nM and 30.9 nM at 25° C; 23.1 nM and 22.9 nM at 0–4° C for the cerebral cortex and heart, respectively. In saturation studies,[3 H] AF-DX 116 labeled 29 percent of the total [3 H](−) QNB binding sites in the cerebral cortical membranes and 87 percent in the cardiac membranes, with K d values of 28.9 nM and 17.9 nM, respectively. Muscarinic antagonists inhibited [3 H] AF-DX 116 binding in a rank order of potency of atropine> dexetimide> AF-DX 116> PZ> levetimide in both tissues. Except for PZ/[3 H] AF-DX 116 and AF-DX 116/[3 H] AF-DX 116 in the cerebral cortex, all the antagonist competition curves had Hill coefficients close to one. Carbachol and oxotremorine produced shallow inhibition curves against [3 H] AF-DX 116 binding in both tissues. Regional distribution studies with [3 H](−) QNB,[3 H] PZ and [3 H] AF-DX 116 showed that most of the muscarinic receptors in the cerebral cortex, hippocampus, nucleus accumbens and corpus striattum are of the M 1 subtype while those in the brainstem, cerebellum and other lower brain regions are of the M 2 subtype. These results indicate that [3 H] AF-DX 116 is a useful probe for the study of heterogeneity of muscarinic cholinergic receptors.
