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.
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.
Authors: Constance N Wilson; Constance O Vance; Timothy M Doyle; David S Brink; George M Matuschak; Andrew J Lechner Journal: Innate Immun Date: 2011-08-23 Impact factor: 2.680
Authors: Constance N Wilson; Constance O Vance; Melissa G Lechner; George M Matuschak; Andrew J Lechner Journal: Eur J Pharmacol Date: 2014-07-18 Impact factor: 4.432
Authors: Tianming Le; John F Eisses; Kathryn L Lemon; John A Ozolek; Derek A Pociask; Abrahim I Orabi; Sohail Z Husain Journal: Pancreas Date: 2015-04 Impact factor: 3.327
Authors: Wei Huang; Matthew C Cane; Rajarshi Mukherjee; Peter Szatmary; Xiaoying Zhang; Victoria Elliott; Yulin Ouyang; Michael Chvanov; Diane Latawiec; Li Wen; David M Booth; Andrea C Haynes; Ole H Petersen; Alexei V Tepikin; David N Criddle; Robert Sutton Journal: Gut Date: 2015-12-07 Impact factor: 23.059