Grady S, Marks M J, Wonnacott S, Collins A C
Institute for Behavioral Genetics, University of Colorado, Boulder 80309.
J Neurochem. 1992 Sep;59(3):848-56. doi: 10.1111/j.1471-4159.1992.tb08322.x.
This study establishes that presynaptic nicotinic receptors modulate dopamine release in the mouse striatum. Nicotinic agonists elicit a dose-dependent increase in the release of [3H]dopamine from synaptosomes prepared from mouse striatum. At low concentrations, this release is Ca2+ dependent, whereas at higher concentrations Ca(2+)-independent, mecamylamine-insensitive release was also observed. The Ca(2+)-dependent nicotine-evoked release was not blocked by alpha-bungarotoxin but was effectively blocked by neuronal bungarotoxin as well as several other nicotinic receptor antagonists. The relationship between potency for stimulation of release for agonists and potency for inhibition of release for antagonists was compared to the affinity of these compounds for the [3H]nicotine binding site. The overall correlation between release and binding potency was not high, but the drugs may be classified into separate groups, each of which has a high correlation with binding. This finding suggests either that more than one nicotinic receptor regulates dopamine release or that not all agonists interact with the same receptor in an identical fashion.
本研究证实，突触前烟碱型受体可调节小鼠纹状体中多巴胺的释放。烟碱型激动剂可使从小鼠纹状体制备的突触体中[3H]多巴胺的释放呈剂量依赖性增加。在低浓度时，这种释放依赖于Ca2+，而在较高浓度时，则观察到不依赖于Ca(2+)、对美加明不敏感的释放。依赖于Ca(2+)的尼古丁诱发的释放不受α-银环蛇毒素的阻断，但可被神经元型银环蛇毒素以及其他几种烟碱型受体拮抗剂有效阻断。将激动剂刺激释放的效力与拮抗剂抑制释放的效力之间的关系，与这些化合物对[3H]尼古丁结合位点的亲和力进行了比较。释放与结合效力之间的总体相关性不高，但这些药物可分为不同的组，每组与结合都有高度相关性。这一发现表明，要么不止一种烟碱型受体调节多巴胺的释放，要么并非所有激动剂都以相同方式与同一受体相互作用。
