Mishra R K, Marcotte E R, Chugh A, Barlas C, Whan D, Johnson R L
Department of Psychiatry, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Peptides. 1997;18(8):1209-15. doi: 10.1016/s0196-9781(97)00147-2.
The present study was undertaken to determine if the previously reported in vitro interactions of the Pro-Leu-Gly-NH2 (PLG) peptidomimetic analogue 3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacet amide (PAOPA) with the dopaminergic system could be exhibited in an in vivo animal model using 6-hydroxydopamine (6-OHDA)-lesioned rats. In this model, PAOPA was found to potentiate the contralateral rotational behavior induced by either apomorphine or L-DOPA. PAOPA was 100-fold more potent than PLG, and produced a fourfold greater response than PLG when administered i.p. PAOPA also potentiated contralateral rotations induced by SKF-38393 and quinpirole. In summary, the results of this study indicate that PAOPA, a conformationally constrained peptidomimetic analogue of PLG, can modulate dopaminergic activity in vivo with higher potency and efficacy than PLG.
本研究旨在确定之前报道的脯氨酸-亮氨酸-甘氨酸-氨基（PLG）拟肽类似物3(R)-[(2(S)-吡咯烷基羰基)氨基]-2-氧代-1-吡咯烷乙酰胺（PAOPA）与多巴胺能系统的体外相互作用，是否能在使用6-羟基多巴胺（6-OHDA）损伤大鼠的体内动物模型中表现出来。在该模型中，发现PAOPA可增强阿扑吗啡或左旋多巴诱导的对侧旋转行为。PAOPA的效力比PLG高100倍，腹腔注射时产生的反应比PLG大四倍。PAOPA还增强了SKF-38393和喹吡罗诱导的对侧旋转。总之，本研究结果表明，PAOPA作为PLG的构象受限拟肽类似物，在体内调节多巴胺能活性的效力和效果比PLG更高。
