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- Title
Activation of Phosphatidylinositol-Linked D<sub>1</sub>-Like Receptor Modulates FGF-2 Expression in Astrocytes via IP3-Dependent Ca<sup>2+</sup> Signaling.
- Authors
Xinhua Zhang; Zheng Zhou; Dakui Wang; Aiqun Li; Yanqing Yin; Xiaosong Gu; Fei Ding; Xuechu Zhen; Jiawei Zhou
- Abstract
Fibroblast growth factor-2 (FGF-2) is predominantly synthesized and secreted by astrocytes in adult brain. Our previous study showed that activation of classical dopamine receptor D1 or D2 elicits FGF-2 biosynthesis and secretion in astrocytes. Here, we report that astrocytic FGF-2 expression is also regulated by phosphatidylinositol (PI)-linked D1-like receptor. SKF83959, a selective PI-linked D1-like receptor agonist, upregulates the levels of FGF-2 protein in striatal astrocyte cultures in classical dopamine D1 and D2 receptorindependent manner. The conditional medium derived from SKF83959-activated astrocytes promoted the number of TH+ neurons in vitro. Treatment of astrocytes with SKF83959 increased intracellular calcium in two phases. Inhibition of intracellular calcium oscillation by inositol 1,4,5-triphosphate (IP3) inhibitors blocked the SKF83959-induced increase in FGF-2 expression. Moreover, intraperitoneal administration of SKF83959 reversed l-methyl-4-phenyl-l,2,3,6-tetrahydropypridine (MPTP)-induced reduction in FGF-2 expression in both the striatum and ventral midbrain and resulted in marked protection of dopaminergic neurons from MPTP-induced neurotoxicity. These results indicate that IP3/Ca2+/calmodulin-dependent protein kinase is an uncharted intracellular signaling pathway that is crucial for the regulation of FGF-2 synthesis in astrocytes. PI-linked D1-like receptor plays an important role in the regulation of astrocytic FGF-2 expression and neuroprotection which may provide a potential target for the drug discovery in Parkinson's disease.
- Subjects
ASTROCYTES; FIBROBLAST growth factors; DOPAMINE; INOSITOL; MESENCEPHALON; PARKINSON'S disease; NEUROTOXICOLOGY
- Publication
Journal of Neuroscience, 2009, Vol 29, Issue 24, p7766
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0389-09.2009