Kommalage Mahinda, Höglund A Urban
Department of Neuroscience, Division of Comparative Medicine, BMC, Uppsala University, Box 572, S-75123, Uppsala, Sweden.
Eur J Pharmacol. 2005 Feb 21;509(2-3):127-34. doi: 10.1016/j.ejphar.2004.12.017.
Stimulation of spinal serotonin (5-HT) receptors results in analgesia and release of acetylcholine. We investigated the involvement of 5-HT1, 5-HT2, and 5-HT3 receptor subtypes in the regulation of spinal acetylcholine release. A spinal microdialysis probe was placed dorsally at about the C5 level in anaesthetized rats. The selective serotonin reuptake inhibitor citalopram was found to increase acetylcholine release when infused via the microdialysis probe. Several doses of the 5-HT receptor agonists 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT, 5-HT1A), 1,4-dihydro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-5H-pyrrolo[3,2-b]pyridin-5-one dihydrochloride (CP93129, 5-HT1B), alpha-methyl-5-hydroxytryptamine maleate (m5-HT, 5-HT2), 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 5-HT2C), and 1-(m-chlorophenyl)-biguanide (5-HT3) were subsequently infused via the microdialysis probe. Only 8-OH-DPAT, CP93129, and m5-HT increased acetylcholine release dose dependently. The 5-HT1A receptor selective antagonist (S)-N-tert-butyl-3-(4-(2-methoxyphenyl)piperazine-1-yl)-2-phenylpropanamide hydrochloride and the 5-HT2A receptor selective antagonist ketanserin tartrate inhibited the 8-OH-DPAT and the m5-HT induced acetylcholine release. The results suggest that 5-HT1A and the 5-HT2A receptors are involved in the regulation of acetylcholine release in the spinal cord.
刺激脊髓5-羟色胺（5-HT）受体可产生镇痛作用并释放乙酰胆碱。我们研究了5-HT1、5-HT2和5-HT3受体亚型在脊髓乙酰胆碱释放调节中的作用。将脊髓微透析探针置于麻醉大鼠的C5水平背侧。发现选择性5-羟色胺再摄取抑制剂西酞普兰通过微透析探针注入时可增加乙酰胆碱释放。随后通过微透析探针注入几种剂量的5-HT受体激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT，5-HT1A）、1,4-二氢-3-（1,（2,3,6-四氢-4-吡啶基）-5H-吡咯并[3,2-b]吡啶-5-酮二盐酸盐（CP93129，5-HT1B）、α-甲基-5-羟色胺马来酸盐（m5-HT，5-HT2）、1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷（DOI，5-HT2C）和1-（间氯苯基）-双胍（5-HT3）。只有8-OH-DPAT、CP93129和m5-HT剂量依赖性地增加乙酰胆碱释放。选择性5-HT1A受体拮抗剂（S）-N-叔丁基-3-（4-（2-甲氧基苯基）哌嗪-1-基）-2-苯基丙酰胺盐酸盐和选择性5-HT2A受体拮抗剂酮色林酒石酸盐抑制8-OH-DPAT和m5-HT诱导的乙酰胆碱释放。结果表明，5-HT1A和5-HT2A受体参与脊髓乙酰胆碱释放的调节。
