TY - JOUR
T1 - Activation of adenosine A1-receptor pathway induces edema formation in the pancreas of rats
AU - Satoh, Akihiko
AU - Shimosegawa, Tooru
AU - Satoh, Kennichi
AU - Ito, Harunobu
AU - Kohno, Yutaka
AU - Masamune, Atsushi
AU - Fujita, Motokazu
AU - Toyota, Takayoshi
PY - 2000/1/1
Y1 - 2000/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033867041&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033867041&partnerID=8YFLogxK
U2 - 10.1053/gast.2000.16502
DO - 10.1053/gast.2000.16502
M3 - Article
C2 - 10982777
AN - SCOPUS:0033867041
VL - 119
SP - 829
EP - 836
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 3
ER -