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Contribution of adenosine A 2 receptors and cyclic adenosine monophosphate to protective ischemic preconditioning of sinusoidal endothelial cells against storage/reperfusion injury in rat livers
Author(s) -
Arai Masahiro,
Thurman Ronald G.,
Lemasters John J.
Publication year - 2000
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2000.8896
Subject(s) - adenosine , ischemic preconditioning , adenosine a1 receptor , adenosine receptor , agonist , adenosine a3 receptor , reperfusion injury , endocrinology , ccpa , medicine , purinergic signalling , endothelial stem cell , cold storage , ischemia , pharmacology , receptor , biology , biochemistry , in vitro , horticulture
A brief period of liver ischemia decreases sinusoidal endothelial cell killing after cold liver storage and improves graft survival after liver transplantation, a phenomenon called ischemic preconditioning. In this study, we investigated the mechanism of sinusoidal endothelial cell protection after ischemic preconditioning. Livers were preconditioned by 5 minutes of ischemia and 5 minutes of reperfusion. Subsequently, livers were stored for 30 hours in cold University of Wisconsin (UW) solution and reperfused briefly with physiological buffer containing Trypan blue. Ischemic preconditioning decreased sinusoidal endothelial cell killing after storage/reperfusion, as assessed by Trypan blue staining of nonparenchymal cells. Adenosine A 2 receptor blockade prevented the protective effect of ischemic preconditioning. By contrast, adenosine A 1 receptor blockade did not prevent protective ischemic preconditioning. Other rat livers were treated with adenosine A 1 and A 2 receptor agonists or dibutyryl–cyclic adenosine monophosphate (DB‐cAMP) before storage. The adenosine A 2 receptor agonist, CGS‐21680, and DB‐cAMP decreased sinusoidal endothelial cell killing to the same extent as ischemic preconditioning, but the adenosine A 1 receptor agonist, 2‐chloro‐ N 6 ‐cyclopentyladenosine (CCPA), had no effect. The adenosine A 2 agonist and prostaglandin E 2 , another agent that preconditions sinusoidal endothelial cells against storage/reperfusion injury, but not the adenosine A 1 agonist, increased cAMP levels in cultured sinusoidal endothelial cells. In conclusion, an adenosine A 2 receptor pathway coupled to increased cAMP mediates sinusoidal endothelial cell protection by ischemic preconditioning.