Prince R J, Fernandes K G, Gregory J C, Martyn I D, Lippiello P M
Integrated Toxicology Program, Duke University Medical Center, Durham, NC 27710, USA.
Biochem Pharmacol. 1996 Aug 23;52(4):613-8. doi: 10.1016/0006-2952(96)00313-9.
The calcium channel subtypes mediating nicotine-evoked [3H]dopamine release from rat striatal synaptosomes were probed with L-, N-, and P-type calcium channel ligands. Responses to nicotine were blocked by the peptides omega-conotoxin GVIA and omega-agatoxin IVA. The affinity constants for these compounds were consistent with their actions at N- and P-type channels, respectively. Together, these channels mediate at least 90% of the calcium-dependent response to nicotine. The L-type antagonists nifedipine, verapamil, and nicardipine were also effective blockers of nicotine-evoked release with maximal effects of 80-100% inhibition. However, these effects occurred at concentrations 2-3 orders of magnitude higher than those necessary to block L-type channels. Moreover, Bay K8644, an L-type agonist, also blocked nicotine-evoked release. Together, these findings argue strongly against the involvement of L-type channels.
利用L型、N型和P型钙通道配体探究了介导尼古丁诱发大鼠纹状体突触体释放[3H]多巴胺的钙通道亚型。对尼古丁的反应被肽ω-芋螺毒素GVIA和ω-阿加毒素IVA阻断。这些化合物的亲和常数分别与其对N型和P型通道的作用一致。这些通道共同介导了至少90%的对尼古丁的钙依赖性反应。L型拮抗剂硝苯地平、维拉帕米和尼卡地平也是尼古丁诱发释放的有效阻断剂，最大抑制作用为80 - 100%。然而，这些作用发生的浓度比阻断L型通道所需的浓度高2 - 3个数量级。此外，L型激动剂Bay K8644也阻断尼古丁诱发的释放。这些发现共同强烈反对L型通道的参与。
