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Balance of purines may determine life or death of retinal ganglion cells as A 3 adenosine receptors prevent loss following P2X 7 receptor stimulation
Author(s) -
Zhang Xiulan,
Zhang Mei,
Laties Alan M.,
Mitchell Claire H.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03900.x
Subject(s) - adenosine , purinergic signalling , adenosine a3 receptor , adenosine receptor , adenosine receptor antagonist , agonist , purinergic receptor , adenosine a2b receptor , adenosine a1 receptor , stimulation , receptor , biology , pharmacology , medicine , endocrinology , chemistry , microbiology and biotechnology , biochemistry
The purines ATP and adenosine can act as a coordinated team of transmitters. As extracellular adenosine is frequently derived from the enzymatic dephosphorylation of released ATP, the distinct actions of the two purines can be synchronized. In retinal ganglion cells (RGCs), stimulation of the P2X 7 receptor for ATP leads to increased intracellular Ca 2+ and death. Here we define the contrasting effects of adenosine and identify protective actions mediated by the A 3 receptor. Adenosine attenuated the rise in Ca 2+ produced by the P2X 7 agonist 3′‐ O ‐(4‐benzoylbenzoyl)ATP (BzATP). Adenosine was also neuroprotective, increasing the survival of ganglion cells exposed to BzATP. The A 3 adenosine receptor agonist 2‐chloro‐ N 6 ‐(3‐iodobenzyl)‐adenosine‐5′‐ N ‐methyluronimide (Cl‐IB‐MECA) mimicked the inhibition of the Ca 2+ rise, whereas the A 3 antagonist 3‐Ethyl‐5‐benzyl‐2‐methyl‐4‐phenylethynyl‐6‐phenyl‐1,4‐(±)‐dihydropyridine‐3,5‐dicarboxylate (MRS‐1191) reduced the protective effects of adenosine. Both Cl‐IB‐MECA and a second A 3 receptor agonist IB‐MECA reduced the cell loss triggered by BzATP. The actions of BzATP were mimicked by ATPγS, but not by ATP. In summary, adenosine can stop the rise in Ca 2+ and cell death resulting from stimulation of the P2X 7 receptor on RGCs, with the A 3 adenosine receptor contributing to this protection. Hydrolysis of ATP into adenosine and perhaps inosine shifts the balance of purinergic action from that of death to the preservation of life.