Antoni F A, Palkovits M, Simpson J, Smith S M, Leitch A L, Rosie R, Fink G, Paterson J M
Medial Research Council Brain Metabolism Unit, University of Edinburgh, Edinburgh, EH8 9JZ, Scotland, United Kingdom.
J Neurosci. 1998 Dec 1;18(23):9650-61. doi: 10.1523/JNEUROSCI.18-23-09650.1998.
Activation of cAMP synthesis by intracellular Ca2+ is thought to be the main mode of cAMP generation in the brain. Accordingly, the Ca2+-activated adenylyl cyclases I and VIII are expressed prominently in forebrain neurons. The present study shows that the novel adenylyl cyclase type IX is inhibited by Ca2+ and that this effect is blocked selectively by inhibitors of calcineurin such as FK506 and cyclosporin A. Moreover, adenylyl cyclase IX is inhibited by the same range of intracellular free Ca2+ concentrations that stimulate adenylyl cyclase I. Adenylyl cyclase IX is expressed prominently in the forebrain. Substantial arrays of neurons positive for AC9 mRNA were found in the olfactory lobe, in limbic and neocortical areas, in the striatum, and in the cerebellar system. These data show that the initiation of the cAMP signal by adenylyl cyclase may be controlled by Ca2+/calcineurin and thus provide evidence for a novel mode of tuning the cAMP signal by protein phosphorylation/dephosphorylation cascades.
细胞内Ca2+激活cAMP合成被认为是大脑中cAMP产生的主要方式。因此，Ca2+激活的腺苷酸环化酶I和VIII在前脑神经元中大量表达。本研究表明，新型腺苷酸环化酶IX受Ca2+抑制，且这种效应被钙调神经磷酸酶抑制剂（如FK506和环孢菌素A）选择性阻断。此外，腺苷酸环化酶IX在与刺激腺苷酸环化酶I相同的细胞内游离Ca2+浓度范围内受到抑制。腺苷酸环化酶IX在前脑大量表达。在嗅叶、边缘和新皮质区域、纹状体以及小脑系统中发现了大量AC9 mRNA阳性神经元。这些数据表明，腺苷酸环化酶引发的cAMP信号可能受Ca2+/钙调神经磷酸酶控制，从而为通过蛋白质磷酸化/去磷酸化级联调节cAMP信号的新模式提供了证据。
