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

Gastroenterology. 2000 Sep;119(3):829-36. doi: 10.1053/gast.2000.16502.


Background & aims: Adenosine has been shown to modulate various pathophysiologic 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 intraperitoneal injections of selective agonists of A1, A2a, and A3 adenosine receptors: 2-chloro-N(6)-cyclopentyladenosine (CCPA), CGS-21680 (CGS), or 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-be ta-D-ribofuranuronamide (IB-MECA), respectively. Serum amylase activity and pathologic changes of the pancreas were evaluated. The effects of a specific A1-receptor antagonist (FK-838) on the pathologic findings of cerulein- and taurocholate-induced pancreatitis were also examined.

Results: Administration of a selective A1 agonist induced hyperamylasemia and morphologic changes in the pancreas characterized by interstitial edema and leukocyte infiltration; neither A2a nor A3 agonist produced such changes. Treatment with an A1-receptor antagonist significantly attenuated the outcome induced by A1 agonist stimulation. In addition, the A1-receptor antagonist significantly ameliorated pancreatic edema in both pancreatitis models, although it did not improve the acinar cell damage of the pancreas or the increase of serum amylase.

Conclusions: Activation of the adenosine A1-receptor pathway may have an important role in the pathogenesis of acute pancreatitis.

MeSH terms

  • Acute Disease
  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacology
  • Amylases / blood
  • Animals
  • Ceruletide
  • Edema / etiology*
  • Edema / pathology
  • Leukocytes / pathology
  • Male
  • Pancreas / pathology
  • Pancreatic Diseases / etiology*
  • Pancreatic Diseases / pathology
  • Pancreatitis / chemically induced
  • Pancreatitis / pathology
  • Phenethylamines / pharmacology
  • Purinergic P1 Receptor Agonists
  • Purinergic P1 Receptor Antagonists
  • Pyrazoles / pharmacology
  • Pyridines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptor, Adenosine A3
  • Receptors, Purinergic P1 / physiology*
  • Taurocholic Acid


  • Phenethylamines
  • Purinergic P1 Receptor Agonists
  • Purinergic P1 Receptor Antagonists
  • Pyrazoles
  • Pyridines
  • Receptor, Adenosine A3
  • Receptors, Purinergic P1
  • 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
  • FK 838
  • N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine
  • 2-chloro-N(6)cyclopentyladenosine
  • Taurocholic Acid
  • Ceruletide
  • Amylases
  • Adenosine