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

Akihiko Satoh, Tooru Shimosegawa, Kennichi Satoh, Harunobu Ito, Yutaka Kohno, Atsushi Masamune, Motokazu Fujita, Takayoshi Toyota

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Abstract

Background and 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-N6-cyclopen-tyladenosine (CCPA), CGS-21680 (CGS), or 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methy l-β-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.

Original languageEnglish
Pages (from-to)829-836
Number of pages8
JournalGastroenterology
Volume119
Issue number3
DOIs
Publication statusPublished - 2000 Jan 1

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Satoh, A., Shimosegawa, T., Satoh, K., Ito, H., Kohno, Y., Masamune, A., Fujita, M., & Toyota, T. (2000). Activation of adenosine A1-receptor pathway induces edema formation in the pancreas of rats. Gastroenterology, 119(3), 829-836. https://doi.org/10.1053/gast.2000.16502