Kiss J P, Windisch K, De Oliveira K, Hennings E C, Mike A, Szász B K
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
Neurochem Res. 2001 Sep;26(8-9):943-50. doi: 10.1023/a:1012384517784.
The aim of this study was to investigate the mechanisms involved in the effect of nicotinic agonists on the [3H]norepinephrine ([3H]NE) release from rat hippocampal slices. The stimulatory effect of nicotine, cytisine, epibatidine and anatoxin-A was completely blocked by the nicotinic antagonist mecamylamine (10 microM). In contrast, the effect of dimethylphenylpiperazinium (DMPP) was only partially inhibited by mecamylamine but was completely blocked by the NE uptake inhibitor desipramine (DMI, 10 microM). Finally, the effect of lobeline was not affected by mecamylamine and was only partially blocked by DMI. Our data indicate that the majority of nicotinic agonists increase the release of [3H]NE exclusively via stimulation of nicotinic acetylcholine receptors (nAChRs). DMPP, in addition to the stimulation of nAChRs, also evokes a carrier-mediated release. Lobeline has no stimulatory effect on nAChRs, induces a carrier-mediated release and has a further action of unidentified mechanism. Our results suggest that special caution is required for the interpretation of data, when DMPP or lobeline are used as nicotinic agonists.
本研究旨在探讨烟碱样激动剂对大鼠海马切片中[3H]去甲肾上腺素（[3H]NE）释放产生影响的相关机制。烟碱、金雀花碱、埃博霉素B和anatoxin - A的刺激作用被烟碱样拮抗剂美加明（10微摩尔）完全阻断。相比之下，二甲基苯基哌嗪鎓（DMPP）的作用仅被美加明部分抑制，但被去甲肾上腺素摄取抑制剂地昔帕明（DMI，10微摩尔）完全阻断。最后，洛贝林的作用不受美加明影响，仅被DMI部分阻断。我们的数据表明，大多数烟碱样激动剂仅通过刺激烟碱型乙酰胆碱受体（nAChRs）来增加[3H]NE的释放。除了刺激nAChRs外，DMPP还引发载体介导的释放。洛贝林对nAChRs无刺激作用，诱导载体介导的释放，且具有一种机制不明的进一步作用。我们的结果表明，当使用DMPP或洛贝林作为烟碱样激动剂时，在数据解释方面需要特别谨慎。
