RGD Reference Report - Activation of adenosine A2A receptor protects sympathetic neurons against nerve growth factor withdrawal. - Rat Genome Database

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Activation of adenosine A2A receptor protects sympathetic neurons against nerve growth factor withdrawal.

Authors: Ramirez, SH  Fan, S  Maguire, CA  Perry, S  Hardiek, K  Ramkumar, V  Gelbard, HA  Dewhurst, S  Maggirwar, SB 
Citation: Ramirez SH, etal., J Neurosci Res. 2004 Jul 15;77(2):258-69.
RGD ID: 1625666
Pubmed: PMID:15211592   (View Abstract at PubMed)
DOI: DOI:10.1002/jnr.20150   (Journal Full-text)

Adenosine mediates a range of effects in the central nervous system (CNS), including the promotion of neuronal survival, but its actions on sympathetic neurons are less well characterized. We therefore sought to understand the role of endogenous adenosine in contributing to the survival of neurotrophin-dependent sympathetic neurons. Rat superior cervical ganglion (SCG) cultures were maintained in the continuous presence of nerve growth factor (NGF) and then exposed to adenosine deaminase (ADA), to deplete endogenous adenosine. This resulted in a marked increase in cellular apoptosis, to a level that approximated the effect of NGF withdrawal. Furthermore, the addition of exogenous adenosine to NGF-deprived SCG neurons resulted in enhanced cell survival. Analysis of adenosine receptor (AR) subtypes on these neurons, using real-time RT-PCR and receptor binding analyses, revealed that the A2A receptor was the major subtype present. Accordingly, the A2A receptor agonist CGS21680 significantly reduced both ADA-induced and NGF-withdrawal-induced neuronal apoptosis, whereas the A1 receptor agonist R-PIA had no such effect. The survival-promoting effect of CGS21680 was eliminated when cells were coincubated with a molar excess of an A2A receptor antagonist. Finally, follow-up experiments revealed that CGS21680 prevented the induction of early apoptotic events, such as changes in mitochondrial integrity and caspase activation, and that it also triggered an increase in ERK activation, which was essential for neurotrophin-independent cell survival. Taken together, these findings provide evidence that endogenous adenosine may be important in mediating protection of sympathetic neurons and that it may act via the A2A receptor subtype.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process  IDA 1625666 RGD 
negative regulation of neuron apoptotic process  IDA 1625666 RGD 
regulation of mitochondrial membrane potential  IDA 1625666prevention of apoptotic mitochondrial membrane hyperpolarizationRGD 

Objects Annotated

Genes (Rattus norvegicus)
Adora2a  (adenosine A2a receptor)


Additional Information