Damsma G, Westerink B H, de Vries J B, Horn A S
Department of Medicinal Chemistry, State University of Groningen, The Netherlands.
Neurosci Lett. 1988 Jul 8;89(3):349-54. doi: 10.1016/0304-3940(88)90551-4.
The effects of cholinergic drugs on the in vivo release of dopamine (DA) and its metabolites were studied in the striatum of freely moving rats. The endogenous compounds were sampled by microdialysis and analysed by on-line HPLC. High doses of oxotremorine (5 mumol/kg), physostigmine (3.6 mumol/kg), nicotine (3 mumol/kg) and atropine (10 mumol/kg) were injected i.p. Oxotremorine, physostigmine and atropine failed to modify the release of DA, while nicotine induced a slight (30%) but significant increase in the release of the transmitter. In contrast, oxotremorine and physostigmine did produce a significant rise of the dialysate contents of the DA metabolites. Thus, these data demonstrate clearly that changes in DA metabolism do not necessarily reflect changes in the release of DA. The most interesting findings of the present study is the fact that muscarinic receptor stimulation or blockade does not modify the release of DA from the rat striatum, while nicotine receptor stimulation may exert some stimulatory effect on the release of DA. This conclusion does not support the concept that the mode of action of anticholinergic drugs used in the treatment of parkinsonism, can be ascribed to a modulation of striatal dopaminergic activity.
在自由活动大鼠的纹状体中研究了胆碱能药物对多巴胺（DA）及其代谢产物体内释放的影响。通过微透析对内源性化合物进行采样，并通过在线高效液相色谱法进行分析。腹腔注射高剂量的氧化震颤素（5 μmol/kg）、毒扁豆碱（3.6 μmol/kg）、尼古丁（3 μmol/kg）和阿托品（10 μmol/kg）。氧化震颤素、毒扁豆碱和阿托品未能改变DA的释放，而尼古丁使递质释放轻微（30%）但显著增加。相反，氧化震颤素和毒扁豆碱确实使DA代谢产物的透析液含量显著升高。因此，这些数据清楚地表明，DA代谢的变化不一定反映DA释放的变化。本研究最有趣的发现是，毒蕈碱受体的刺激或阻断不会改变大鼠纹状体中DA的释放，而尼古丁受体的刺激可能对DA的释放产生一些刺激作用。这一结论不支持将用于治疗帕金森病的抗胆碱能药物的作用方式归因于对纹状体多巴胺能活性的调节这一概念。
