Activation of adenosine A1-receptor pathway induces edema formation in thepancreas of rats

Background & Aims: Adenosine has been shown to modulate various pathophysio logic conditions through receptor-mediated mechanisms. However, the role of adenosine in the pathogenesis of acute pancreatitis has not been described . We examined the effect of adenosine-receptor stimulation or inhibition on the pathologic changes of the pancreas. Methods: Rats received intraperito neal injections of selective agonists of A1, A2a, and A3 adenosine receptor s: 2-chloro-N-6-cyclopentyladenosine (CCPA), CGS-21680 (CGS), or 1-deoxy-1- [6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl] -N-methyl-beta-D-ribofuranu ronamide (IB-MECA), respectively. Serum amylase activity and pathologic cha nges of the pancreas were evaluated. The effects of a specific A1-receptor antagonist (FK-838) on the pathologic findings of cerulein- and taurocholat e-induced pancreatitis were also examined. Results: Administration of a sel ective A1 agonist induced hyperamylasemia and morphologic changes in the pa ncreas characterized by interstitial edema and leukocyte infiltration; neit her A2a nor A3 agonist produced such changes, Treatment with an A1-receptor antagonist significantly attenuated the outcome induced by A1 agonist stim ulation. In addition, the A1-receptor antagonist significantly ameliorated pancreatic edema in both pancreatitis models, although it did not improve t he acinar cell damage of the pancreas or the increase of serum amylase, Con clusions: Activation of the adenosine A1-receptor pathway may have an impor tant role in the pathogenesis of acute pancreatitis.