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Role of adenosine A2A receptor in ischemia reperfusion injury: signaling to extracellular signal‐regulated protein kinase (663.6)
Author(s) -
Atef Reham,
Agha Azza,
Nassar Noha
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.663.6
Subject(s) - agonist , adenosine , adenosine a2a receptor , ischemia , adenosine receptor , adenosine a1 receptor , pharmacology , adenosine a3 receptor , hippocampus , receptor , medicine , chemistry , endocrinology
Adenosine is a potent biological mediator, the concentration of which increases dramatically following brain ischemia. Out of the four known adenosine receptor subtypes (A 1 , A 2A , A 2B and A 3 ), the A 2A is of critical importance in stroke. Although, both A 2A agonists and antagonists are proven protective during ischemia reperfusion (IR) injury, however, ,the mechanisms by which A 2A receptors are noxious during IR remain elusive. The objective of the present study was to investigate the role of central A 2A receptor in modulating cellular as well as behavioral responses to IR injury and the possible involvement of ERK signalling pathway. Hence, we hereby report that bilateral carotid occlusion for 45 min followed by 24h reperfusion period resulted in a significant memory impairment, motor incoordination as well as increased locomotor activity that were not affected by unilateral intrahippocampal injection of a selective A 2A agonist CGS21680, but conversely mitigated by the selective A 2A antagonist SCH58261. On the cellular level, IR increased the pERK, NF k B, cytochrome c, BDNF, Nrf2 and TNF‐α content in the hippocampus. With the exception of Nrf2 level, treatment with SCH58261 significantly reversed these effects, however, CGS21680 treatment resulted in a non‐significant change from IR insult. Accordingly these results suggest a possible protective role of the central A 2A receptor blockade in IR injury with a prospective involvement of p42/44 pathway.