Striatal muscarinic receptors: regulation by dopaminergic agonists.
Striatal muscarinic receptors: regulation by dopaminergic agonists.
复制标题
纹状体毒蕈碱受体：多巴胺能激动剂的调节。
DOI：
10.1016/0024-3205(81)90512-9
复制
发表时间：
1981
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：
Ehlert,FJ;Roeske,WR;Yamamura,HI
用特异性M受体拮抗剂[~3H](−)-3-奎宁基苯甲酸酯([~3H](−)QNb)研究阿朴吗啡对纹状体M受体结合特性的影响。在含镁离子的50 mM钠/HEPES缓冲液(pH 7.4)中进行结合测量时，[~3H](−)QNb的结合符合两个结合部位的存在，57%的结合部位具有0.030 nM的高亲和力解离常数，而其余的结合部位的低亲和解离常数为0.64 nM。阿朴吗啡(1.0μM)通过明显地将低亲和力部位转换为高亲和力部位来增强[~3H](−)QNb的结合。不同的其他药物被筛选以增强[~3H](−)QNb结合的能力，并观察到大体上与多巴胺能效应一致的模式，尽管一些证据表明β-肾上腺素能效应。强效抗神经药氟哌啶醇、螺环酮和舒必利不能拮抗阿朴吗啡对[~3H](−)QNB结合的增强作用，也不能拮抗部分肾上腺素能拮抗剂。然而，多巴胺敏感的腺苷环化酶的强效抑制剂α-flupenthixol和氟奋乃静可特异性地阻断[~3H](−)QNB与阿朴吗啡结合的增强作用，Ki值约为0.1μM。
The effects of apomorphine on the binding properties of striatal muscarinic receptors were investigated using the specific muscarinic antagonist, [3H](−)3-quinuclidinyl benzilate ([3H](−)QNB). When binding measurements were made in 50 mM sodium/HEPES buffer, pH 7.4, containing Mg+2, the binding of [3H](−)QNB was consistent with the presence of two binding sites; 57% of the sites had a high affinity dissociation constant of 0.030 nM whereas the remaining sites had a low affinity dissociation constant of 0.64 nM. Apomorphine (1.0 μM) enhanced the binding of [3H](−)QNB by an apparent conversion of low to high affinity sites. A variety of other agents were screened for their ability to enhance [3H](−)QNB binding, and a pattern generally consistent with a dopaminergic effect was observed although some evidence for a β-adrenergic effect was demonstrable. The potent neuroleptics haloperidol, spiperone and sulpiride failed to antagonize the apomorphine enhancement of [3H](−)QNB binding as well as some adrenergic antagonists. However, the potent inhibitors of the dopamine-sensitive adenylate cyclase, α-flupenthixol and fluphenazine, specifically blocked the apomorphine enhancement of [3H](−)QNB binding with Kivalues of approximately 0.1 μM.