Nakamura S, Goshima Y, Yue J L, Miyamae T, Misu Y
Department of Pharmacology, Yokohama City University School of Medicine, Japan.
Eur J Pharmacol. 1992 Nov 3;222(1):75-80. doi: 10.1016/0014-2999(92)90465-g.
Microdialysis and high performance liquid chromatography with an electrochemical detector were applied to compare the characteristics of nicotine-evoked release of endogenous 3,4-dihydroxyphenylalanine (DOPA) from striata of conscious rats and those of the release of dopamine (DA). Dialysates were collected every 20 min 3-8 h after the start of perfusion. Nicotine was perfused for 20 min through a probe. (+/-)-Nicotine (100-300 microM) constantly and repeatedly released DOPA and DA over a similar time course in a dose-dependent manner. The ratio of the DOPA and DA release evoked was approximately 1:3. The (+/-)-nicotine (200 microM)-induced DOPA release was mecamylamine (500 microM)-sensitive, tetrodotoxin (100 nM)-sensitive and Ca2+ (removal plus 12.5 mM Mg2+ addition)-dependent. The (+)-isomer produced no DOPA release. These characteristics of DOPA release were almost the same as those of DA release. Furthermore, mecamylamine alone inhibited the basal release of DOPA but not of DA. Nicotine released stereoselectively endogenous DOPA via nicotinic acetylcholine receptors from striata of freely moving rats in a manner similar to transmitter DA. These acetylcholine receptors function tonically for the release of DOPA. These findings are further support for our proposal that DOPA is an endogenous neuroactive substance.
采用微透析技术和配备电化学检测器的高效液相色谱法，比较清醒大鼠纹状体中尼古丁诱发内源性3,4 - 二羟基苯丙氨酸（DOPA）释放的特征与多巴胺（DA）释放的特征。在灌注开始后3 - 8小时内，每20分钟收集一次透析液。通过探针将尼古丁灌注20分钟。（±）-尼古丁（100 - 300微摩尔）在相似的时间进程中以剂量依赖的方式持续且反复地释放DOPA和DA。诱发的DOPA和DA释放的比例约为1:3。（±）-尼古丁（200微摩尔）诱导的DOPA释放对美加明（500微摩尔）敏感、对河豚毒素（100纳摩尔）敏感且依赖于Ca2 +（去除外加12.5毫摩尔Mg2 +）。（+）-异构体不产生DOPA释放。DOPA释放的这些特征与DA释放的特征几乎相同。此外，单独使用美加明可抑制DOPA的基础释放，但不抑制DA的基础释放。尼古丁通过烟碱型乙酰胆碱受体从自由活动大鼠的纹状体中立体选择性地释放内源性DOPA，其方式类似于递质DA。这些乙酰胆碱受体对DOPA的释放具有紧张性作用。这些发现进一步支持了我们关于DOPA是一种内源性神经活性物质的提议。
