Dickenson A H, Sullivan A F, Fournie-Zaluski M C, Roques B P
Brain Res. 1987 Apr 7;408(1-2):185-91. doi: 10.1016/0006-8993(87)90370-2.
The enkephalins, found in high levels in the superficial dorsal horn where they are associated with the terminals of afferent nociceptive fibres, are rapidly degraded by at least 3 peptidases. The use of inhibitors of these peptidases allows effects mediated by endogenous enkephalins to be observed. We report here the inhibitory effects on spinal nociceptive transmission of bestatin, a non-specific aminopeptidase inhibitor, thiorphan, an inhibitor of enkephalinase and kelatorphan, a mixed inhibitor of aminopeptidases, particularly aminopeptidase M, enkephalinase and dipeptidylaminopeptidase. The agents were applied intrathecally, directly onto the spinal cord, in halothane-anaesthetized intact rats. Bestatin (n = 23 neurones) produced weak inhibitions of C-fibre-evoked activity (maximum 17% inhibition) whereas thiorphan (n = 20) produced maximal 25% inhibitions. Kelatorphan (n = 32) produced maximal 46% inhibitions which were naloxone reversible. All 3 agents caused dose-dependent effects which were relatively selective for C-fibre evoked responses, sparing A beta-fibre inputs. The results are discussed in relation to roles of the enkephalins in sensory modulation and the potential of these compounds as novel therapeutic agents.
脑啡肽在浅表背角中含量很高，与传入伤害性纤维的终末相关，它会被至少3种肽酶迅速降解。使用这些肽酶的抑制剂能够观察到内源性脑啡肽介导的效应。我们在此报告了最佳抑素（一种非特异性氨肽酶抑制剂）、硫氧还蛋白（一种脑啡肽酶抑制剂）和凯拉托品（一种氨肽酶的混合抑制剂，特别是氨肽酶M、脑啡肽酶和二肽基氨肽酶）对脊髓伤害性传递的抑制作用。这些药物通过鞘内注射，直接作用于脊髓，实验对象为氟烷麻醉的完整大鼠。最佳抑素（n = 23个神经元）对C纤维诱发的活动产生微弱抑制（最大抑制率为17%），而硫氧还蛋白（n = 20）产生的最大抑制率为25%。凯拉托品（n = 32）产生的最大抑制率为46%，且可被纳洛酮逆转。所有这3种药物都产生剂量依赖性效应，对C纤维诱发的反应具有相对选择性，对Aβ纤维输入影响较小。我们结合脑啡肽在感觉调制中的作用以及这些化合物作为新型治疗药物的潜力对结果进行了讨论。
