Herrera-Marschitz M, Hökfelt T, Ungerstedt U, Terenius L, Goldstein M
Eur J Pharmacol. 1984 Jul 13;102(2):213-27. doi: 10.1016/0014-2999(84)90253-x.
Peptides deriving from the proenkephalin B precursor were studied in the Ungerstedt rotational model after their unilateral injection into the substantia nigra. Dynorphin (DYN)-(1-17), DYN-(1-13) and DYN-(1-8) in 0.1-10 micrograms doses induced marked contralateral rotation. This effect was enhanced by subsequent systemic administration of D-amphetamine and blocked by previous treatment with naloxone. alpha-Neoendorphin produced similar effects although there was no evidence for dose-dependency. DYN-(6-17) which lacks opioid activity also produced contralateral rotation, which, however, was not naloxone reversible and D-amphetamine given subsequently did not induce asymmetric activation. Methionine enkephalin and leucine enkephalin, deriving from the proenkephalin A precursor were tested for comparison. Only the former produced weak contralateral rotation. GABA injected at the same site as DYN-(1-17) also induced contralateral rotation which was mimicked by nanogram doses of the gabaergic agonist muscimol. These findings suggest an interaction between peptides from the proenkephalin B precursor and nigro-striatal dopamine neurons as well as gabaergic striato-nigral efferents and/or interneurons.
将源自脑啡肽原B前体的肽单侧注射到黑质后,在昂格斯泰德旋转模型中对其进行了研究。剂量为0.1 - 10微克的强啡肽(DYN)-(1 - 17)、DYN-(1 - 13)和DYN-(1 - 8)可诱导明显的对侧旋转。随后全身给予右旋苯丙胺可增强这种效应,而预先用纳洛酮治疗则可阻断这种效应。α-新内啡肽产生了类似的效应,尽管没有剂量依赖性的证据。缺乏阿片样活性的DYN-(6 - 17)也产生了对侧旋转,然而,这种旋转不能被纳洛酮逆转,随后给予的右旋苯丙胺也不会诱导不对称激活。为作比较,对源自脑啡肽原A前体的甲硫氨酸脑啡肽和亮氨酸脑啡肽进行了测试。只有前者产生了微弱的对侧旋转。在与DYN-(1 - 17)相同的部位注射γ-氨基丁酸(GABA)也可诱导对侧旋转,纳克剂量的GABA能激动剂蝇蕈醇可模拟这种旋转。这些发现表明,脑啡肽原B前体的肽与黑质-纹状体多巴胺神经元以及GABA能纹状体-黑质传出纤维和/或中间神经元之间存在相互作用。