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Brain Res Mol Brain Res ; 112(1-2): 53-60, 2003 Apr 10.
Article in English | MEDLINE | ID: mdl-12670702

ABSTRACT

C3a and C5a anaphylatoxins are two proinflammatory peptides generated during complement system activation. C3a and C5a exert several biological activities through binding to their specific receptors, named C3aR and C5aR, respectively. We have previously shown that C3aR and C5aR are constitutively expressed by astrocytes, a cell type that actively participates in inflammatory events in the central nervous system. In this article, we focus on the transduction signal pathways activated by these two receptors on astrocytes. We show that the stimulation of C3aR or C5aR results in the activation of the mitogen activated protein kinase pathway by phosphorylation of the p44 and p42 kinases. On the contrary, the binding of C3a or C5a to their receptors on astrocytes decreases the production of cAMP, revealing an inhibition of the adenylyl cyclase pathway. Stimulation of C3aR and C5aR induces an increase in intracellular calcium concentration, arising from the opening of intracellular calcium channels. The observed calcium wave results from the activation of the phospholipase C pathway. Taken together, our results suggest that the binding of C3a or C5a to their receptors on astrocytes would be of functional importance since it induces the activation of two important transduction pathways leading to several cellular events such as neurotrophin and cytokine production.


Subject(s)
Astrocytes/metabolism , Brain/metabolism , Complement C3a/metabolism , Complement C5a/metabolism , Cyclic AMP/biosynthesis , MAP Kinase Signaling System/physiology , Signal Transduction/physiology , Adenylyl Cyclases/drug effects , Adenylyl Cyclases/metabolism , Astrocytes/drug effects , Calcium/metabolism , Calcium Signaling/drug effects , Calcium Signaling/physiology , Complement C3a/analogs & derivatives , Complement C3a/pharmacology , Complement C5a/pharmacology , Encephalitis/metabolism , Humans , MAP Kinase Signaling System/drug effects , Mitogen-Activated Protein Kinase 1/drug effects , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3 , Mitogen-Activated Protein Kinases/drug effects , Mitogen-Activated Protein Kinases/metabolism , Protein Binding/drug effects , Protein Binding/physiology , Signal Transduction/drug effects , Tumor Cells, Cultured , Up-Regulation/drug effects , Up-Regulation/physiology
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