Guzman R G, Kendrick K M, Emson P C
Department of Physiology, Faculty of Medicine, National University of Mexico, Mexico City.
Brain Res. 1993 Sep 17;622(1-2):147-54. doi: 10.1016/0006-8993(93)90813-3.
In vivo microdialysis in urethane anaesthetised rats was used to investigate the effects of substance P (SP) on acetylcholine (ACh) and dopamine (DA) release in the rat striatum. Results showed that SP elicited a dose-dependent increase in ACh release between 1 and 50 pmol/l. The rise in ACh release occurred both during SP administration and for up to 60 min after it. Dose-response curves either based on the initial rise in ACh release, or the total duration of increased release, showed a bell shape with 100 fmol/l and 5 nmol/l doses failing to significantly alter release and a 500 pM dose being less effective than 50 pmol/l. In contrast to this, SP did not significantly alter DA release at doses ranging between 100 fmol/l and 5 nmol/l. There was evidence for a strong desensitisation effect of SP administration since after initial treatment with SP subsequent doses of the peptide, even at very high doses, failed to provoke further changes in ACh still showed the expected increase in release in response to a potassium challenge. Physalaemin and neurokinin A increased ACh release with a similar potency to SP at a 50 pmol/l dose whereas neurokinin B and neuropeptide gamma, while increasing ACh release at a 50 pmol/l dose, were less potent than SP. The effect of SP on ACh release is probably mediated via NK-1 receptors since ACh release in response to SP was reduced in a dose dependent manner by the NK-1 receptor antagonists CP-96,345 and RP-67580.
在乌拉坦麻醉的大鼠中进行体内微透析，以研究P物质（SP）对大鼠纹状体中乙酰胆碱（ACh）和多巴胺（DA）释放的影响。结果显示，在1至50 pmol/l之间，SP引起ACh释放呈剂量依赖性增加。ACh释放的增加在SP给药期间以及给药后长达60分钟内均会发生。基于ACh释放的初始增加或释放增加的总持续时间的剂量反应曲线呈钟形，100 fmol/l和5 nmol/l剂量未能显著改变释放，而500 pM剂量的效果不如50 pmol/l。与此相反，在100 fmol/l至5 nmol/l的剂量范围内，SP并未显著改变DA的释放。有证据表明SP给药具有强烈的脱敏作用，因为在用SP进行初始治疗后，后续剂量的该肽即使在非常高的剂量下也未能引发ACh的进一步变化，但对钾刺激仍显示出预期的释放增加。在50 pmol/l剂量下， Physalaemin和神经激肽A增加ACh释放的效力与SP相似，而神经激肽B和神经肽γ虽然在50 pmol/l剂量下增加ACh释放，但效力低于SP。SP对ACh释放的作用可能是通过NK-1受体介导的，因为NK-1受体拮抗剂CP-96,345和RP-67580以剂量依赖的方式降低了对SP的ACh释放反应。
