Kommalage Mahinda, Höglund A Urban
Department of Neuroscience, Division of Comparative Medicine, Uppsala University, BMC, Box 572, S-75123, Uppsala, Sweden.
Eur J Pharmacol. 2005 Nov 21;525(1-3):69-73. doi: 10.1016/j.ejphar.2005.08.035. Epub 2005 Nov 16.
It has been shown that analgesics such as morphine, lidocaine and clonidine increase the release of spinal acetylcholine. Acetylcholine may therefore play an important role in the regulation of spinal pain threshold. Since behavioral as well as in vitro studies have shown a clear involvement of GABA (gamma-amino butyric acid) receptors in the regulation of spinal nociceptive mechanisms, the present study focused on the role of GABA receptors for spinal acetylcholine release control. GABA receptor agonists and antagonists were infused via a spinal microdialysis probe and acetylcholine release was measured. The GABA(A) receptor agonist muscimol decreased acetylcholine release and the antagonist bicuculline increased acetylcholine release. The GABA(B) receptor agonist baclofen decreased acetylcholine release whereas the antagonist saclofen did not change acetylcholine release. The results suggest that both GABA receptor subtypes have an inhibitory role on spinal dorsal horn acetylcholine release and that the GABA(A) receptors are tonically regulating acetylcholine release.
已表明，吗啡、利多卡因和可乐定等镇痛药会增加脊髓乙酰胆碱的释放。因此，乙酰胆碱可能在脊髓痛阈调节中发挥重要作用。由于行为学及体外研究均已表明γ-氨基丁酸（GABA）受体明显参与脊髓伤害性感受机制的调节，故本研究聚焦于GABA受体对脊髓乙酰胆碱释放控制的作用。通过脊髓微透析探针注入GABA受体激动剂和拮抗剂，并测量乙酰胆碱的释放。GABA(A)受体激动剂蝇蕈醇降低了乙酰胆碱的释放，而拮抗剂荷包牡丹碱增加了乙酰胆碱的释放。GABA(B)受体激动剂巴氯芬降低了乙酰胆碱的释放，而拮抗剂沙氯芬未改变乙酰胆碱的释放。结果表明，两种GABA受体亚型对脊髓背角乙酰胆碱的释放均具有抑制作用，且GABA(A)受体对乙酰胆碱的释放具有紧张性调节作用。
