Toms N J, Roberts P J
Department of Pharmacology, University of Bristol, UK.
Eur J Pharmacol. 1994 Jan 1;266(1):63-6. doi: 10.1016/0922-4106(94)90210-0.
The effect of intracellular cyclic AMP (cAMP) on N-methyl-D-aspartate (NMDA) receptor-mediated stimulation of nitric oxide (NO) formation was investigated in rat cerebellar slices. Forskolin (30-120 microM), while lacking any direct effect on NO production, elicited a concentration-dependent enhancement of the response to 10 microM NMDA. Dideoxyforskolin, which does not activate adenylyl cyclase did not influence the NMDA response. Increasing intracellular cAMP directly by incubation with the membrane-permeant analogue of cAMP, 2'-o-dibutyryladenosine 3'5'-cyclic monophosphate (dibutyryl cAMP) (1 mM), similarly enhanced NO formation, as did prevention of cAMP degradation with the phosphodiesterase inhibitor theophylline. The enhancement of NMDA activity appeared to involve protein phosphorylation (possibly of the receptor itself) since the protein kinase A inhibitor H-89, abolished the enhancements with both forskolin and dibutyryl cAMP. Thus cAMP may have a physiological role in the modulation of NMDA receptor-stimulated synthesis of NO.
在大鼠小脑切片中研究了细胞内环状腺苷一磷酸（cAMP）对N-甲基-D-天冬氨酸（NMDA）受体介导的一氧化氮（NO）生成刺激作用的影响。福斯高林（30 - 120微摩尔）虽然对NO生成没有任何直接影响，但却能引起对10微摩尔NMDA反应的浓度依赖性增强。不能激活腺苷酸环化酶的双脱氧福斯高林对NMDA反应没有影响。通过与cAMP的膜渗透性类似物2'-O-二丁酰腺苷3',5'-环磷酸单酯（二丁酰cAMP）（1毫摩尔）一起孵育直接增加细胞内cAMP，与用磷酸二酯酶抑制剂茶碱防止cAMP降解一样，同样增强了NO的生成。NMDA活性的增强似乎涉及蛋白质磷酸化（可能是受体本身的磷酸化），因为蛋白激酶A抑制剂H-89消除了福斯高林和二丁酰cAMP的增强作用。因此，cAMP可能在调节NMDA受体刺激的NO合成中具有生理作用。
