The phosphoprotein DARPP-32 mediates cAMP-dependent potentiation of striatal N-methyl-D-aspartate responses
The phosphoprotein DARPP-32 mediates cAMP-dependent potentiation of striatal N-methyl-D-aspartate responses
复制标题
DOI：
10.1073/pnas.94.26.14859
复制
发表时间：
1997-12-23
影响因子：
11.1
通讯作者：
Spiess, J
中科院分区：
文献类型：
--
作者：
Blank, T;Nijholt, I;Spiess, J
用双电极电压钳技术研究了纹状体N-甲基-D-天冬氨酸(NMDA)反应中cAMP依赖的信号转导途径。在注射大鼠纹状体Poly(A)(+)mRNA的卵母细胞中，Forsklin激活cAMP依赖的蛋白激酶(PKA)增强了NMDA反应，特异性抑制剂Calyculin A抑制蛋白磷酸酶1(PP1)和/或蛋白磷酸酶2A(PP2A)阻断了PKA介导的纹状体NMDA反应的增强，提示PKA的作用是通过抑制蛋白磷酸酶来介导的。同时注射纹状体mRNA和针对蛋白磷酸酶抑制剂DARPP-32的反义寡核苷酸可显著降低PKA对NMDA反应的增强作用。注射大鼠海马PolyA(+)mRNA的卵母细胞记录的NMDA反应不受PKA刺激的影响，当卵母细胞与大鼠海马PolyA(+)mRNA和编码DARPP-32的互补RNA共同注射时，PKA刺激后NMDA反应增强。结果表明，纹状体中丰富的DARPP-32可能参与纹状体两条主要传入通路谷氨酸能和多巴胺能投射之间的信号传递，这可能是通过cAMP依赖的纹状体NMDA电流调节实现的。
The signal transduction pathway underlying the cAMP-dependent modulation of rat striatal N-methyl-D-aspartate (NMDA) responses was investigated by using the two-electrode voltage-clamp technique, In oocytes injected with rat striatal poly(A)(+) mRNA, activation of cAMP-dependent protein kinase (PKA) by forskolin potentiated NMDA responses, Inhibition of protein phosphatase 1 (PP1) and/or protein phosphatase 2A (PP2A) by the specific inhibitor calyculin A occluded the PKA-mediated potentiation of striatal NMDA responses, suggesting that the PKA effect was mediated by inhibition of a protein phosphatase. Coinjection of oocytes with striatal mRNA and antisense oligodeoxynucleotides directed against the protein phosphatase inhibitor DARPP-32 dramatically reduced the PKA enhancement of NMDA responses, NMDA responses recorded from oocytes injected with rat hippocampal poly(A)(+) mRNA were not affected by stimulation of PKA, When oocytes were coinjected with rat hippocampal poly(A)(+) mRNA plus complementary RNA coding for DARPP-32, NMDA responses were potentiated after stimulation of PKA, The results provide evidence that DARPP-32, which is enriched in the striatum, may participate in the signaling between the two major afferent striatal pathways, the glutamatergic and the dopaminergic projections, by the cAMP-dependent regulation of striatal NMDA currents.