Oh J D, Del Dotto P, Chase T N
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Neurosci Lett. 1997 May 30;228(1):5-8. doi: 10.1016/s0304-3940(97)00355-8.
Chronically administered levodopa, the standard treatment for Parkinson's disease, is ultimately associated with disabling alterations in motor response. To evaluate the possible contribution of striatal cAMP-dependent protein kinase A (PKA) signaling pathways to these response modifications, the acute effects of a PKA inhibitor, Rp-cAMPS, on motor response changes attending chronic, twice-daily administration of levodopa were measured in 6-hydroxydopamine lesioned hemi-parkinsonian rats. A single intrastriatal injection of Rp-cAMPS (2.5 or 25 microg) attenuated both the shortened duration and augmented intensity of levodopa-induced turning in a dose dependent manner. Rp-cAMPS completely normalized motor responses to a dopamine D1 agonist (SKF 38392), but had no effect on those to a dopamine D2 agonist (quinpirole). These results suggest that D1 receptor-mediated PKA activation may contribute to the development of the altered motor responses associated with chronic levodopa treatment.
长期服用左旋多巴作为帕金森病的标准治疗方法，最终会导致运动反应出现致残性改变。为了评估纹状体环磷酸腺苷（cAMP）依赖性蛋白激酶A（PKA）信号通路对这些反应改变的可能作用，在6-羟基多巴胺损伤的半帕金森病大鼠中，测量了PKA抑制剂Rp-cAMPS对每日两次长期服用左旋多巴时运动反应变化的急性影响。纹状体内单次注射Rp-cAMPS（2.5或25微克）以剂量依赖性方式减弱了左旋多巴诱导的旋转持续时间缩短和强度增强。Rp-cAMPS使对多巴胺D1激动剂（SKF 38392）的运动反应完全恢复正常，但对多巴胺D2激动剂（喹吡罗）的运动反应没有影响。这些结果表明，D1受体介导的PKA激活可能促成了与长期左旋多巴治疗相关的运动反应改变的发生。
