Unit of Physiology, Department of Health Sciences, University of Jaén, 23071 Jaén, Spain.
Institute of Neurosciences, "Federico Olóriz" University of Granada, Granada, Spain.
Pharmacol Biochem Behav. 2019 Jul;182:12-21. doi: 10.1016/j.pbb.2019.05.007. Epub 2019 May 23.
Aminopeptidase A is responsible for the hydrolysis of angiotensin II and cholecystokinin. By measuring its activity we obtain a reflection of the functional status of its endogenous substrates. Dopamine coexists with these neuropeptides in striatum and prefrontal cortex. If the content of any of them is altered, the others and the functions they are involved in would also be affected. Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) are rat models with different motor behavior and mood. We hypothesized that aminopeptidase A activity could be modified in WKY or SHR affecting the brain dopamine. The results may provide new insights for the understanding of dopamine-related disorders such as schizophrenia, depression or Parkinson's disease. To analyze the influence of unilateral depletions of dopamine on the intra- and inter-hemispheric behavior of aminopeptidase A in striatum and prefrontal cortex of WKY and SHR, aminopeptidase A activity was measured fluorometrically, using an arylamide derivative as substrate, in the left and right sides of striatum and prefrontal cortex of WKY and SHR treated with saline (control groups) or following left or right intrastriatal injections of 6-hydroxydopamine (lesioned groups). Differential asymmetrical intra- and inter-hemispheric behaviors of aminopeptidase A were observed, depending on the lesioned hemisphere, the region and the strain analyzed. Results also demonstrated differential intra and inter-hemispheric correlations between striatum and prefrontal cortex and between both regions and motor behavior depending on the side of lesion. The changes mostly involved the left hemisphere. The functions in which the aminopeptidase A activity is involved could be modified depending on whether the dopamine depletion occurs on the left or right hemisphere.
氨基肽酶 A 负责血管紧张素 II 和胆囊收缩素的水解。通过测量其活性,我们可以反映其内源性底物的功能状态。多巴胺与这些神经肽在纹状体和前额叶皮层共存。如果其中任何一种物质的含量发生改变,其他物质及其参与的功能也会受到影响。Wistar Kyoto (WKY) 和自发性高血压大鼠 (SHR) 是运动行为和情绪不同的大鼠模型。我们假设氨基肽酶 A 活性可能在 WKY 或 SHR 中发生改变,从而影响大脑中的多巴胺。这些结果可能为理解与多巴胺相关的疾病(如精神分裂症、抑郁症或帕金森病)提供新的见解。为了分析单侧多巴胺耗竭对 WKY 和 SHR 纹状体和前额叶皮层中氨基肽酶 A 的内外侧行为的影响,我们使用芳酰胺衍生物作为底物,通过荧光法测量了 WKY 和 SHR 左侧和右侧纹状体和前额叶皮层中氨基肽酶 A 的活性,这些 WKY 和 SHR 接受了生理盐水(对照组)或左侧或右侧纹状体内注射 6-羟多巴胺(损伤组)的处理。观察到依赖于损伤半球、区域和分析的菌株的氨基肽酶 A 的不同不对称内外侧行为。结果还表明,根据损伤侧,纹状体和前额叶皮层之间以及这两个区域与运动行为之间存在不同的内外侧相关性。这些变化主要涉及左侧半球。取决于多巴胺耗竭发生在左侧还是右侧半球,氨基肽酶 A 活性所涉及的功能可能会发生改变。