Wolterink G, van Ree J M, van Nispen J W, de Wied D
Rudolf Magnus Institute, Faculty of Medicine, University of Utrecht, The Netherlands.
Life Sci. 1991;48(2):155-61. doi: 10.1016/0024-3205(91)90409-5.
The behavioral effects of two peptides (HOE 427) and ORG 31433) related to the ACTH-(4-9) analog ORG 2766 were investigated in Wistar rats in a number of tests in which Org 2766 is active. Subcutaneous administration of HOE 427 in a dose of 0.5 ng/kg or ORG 31433 in doses of 0.5-5.0 ng/kg facilitated passive avoidance behavior whereas these peptides attenuated the avoidance response in doses of 25 ng/kg and 250 ng/kg respectively. ORG 31433 (0.1 - 1.0 microgram/kg) decreased motor activity of group housed rats tested under low light conditions. Furthermore subcutaneous (1.0- 10.0 ng/kg) or oral (10 microgram/kg) administration of ORG 31433 accelerated functional recovery from 6-hydroxydopamine (6-OHDA)-induced lesions in the nucleus accumbens which cause motor hypoactivity. The experiments show that as compared to ORG 2766 the peptides HOE 427 and ORG 31433 induce qualitatively similar responses but are approximately 10 to 100 times more potent. These data may imply that substitution of the C-terminal COOH group of ORG 2766 yields neuropeptides with increased potency.
在一些ORG 2766具有活性的试验中，研究了与促肾上腺皮质激素（4-9）类似物ORG 2766相关的两种肽（HOE 427和ORG 31433）对Wistar大鼠的行为影响。皮下注射0.5 ng/kg剂量的HOE 427或0.5 - 5.0 ng/kg剂量的ORG 31433可促进被动回避行为，而这些肽分别在25 ng/kg和250 ng/kg剂量时会减弱回避反应。ORG 31433（0.1 - 1.0微克/千克）可降低在弱光条件下测试的群居大鼠的运动活性。此外，皮下注射（1.0 - 10.0 ng/kg）或口服（10微克/千克）ORG 31433可加速伏隔核中由6-羟基多巴胺（6-OHDA）诱导损伤所致的功能恢复，该损伤会导致运动活动减退。实验表明，与ORG 2766相比，肽HOE 427和ORG 31433诱导的反应在性质上相似，但效力大约高10至100倍。这些数据可能意味着ORG 2766的C末端COOH基团被取代后会产生效力增强的神经肽。
