Effect of long-term CCK blockade on the pancreatic acinar cell renewal in rats with acute pancreatitis.
This study determines the effect of 7-day pretreatment with L364,718 (a potent cholecystokinin (CCK) receptor antagonist) on pancreatic cell turnover during the course of acute pancreatitis (AP) induced in the rat by bile-pancreatic duct obstruction (BPDO). Cell cycle distribution and apoptosis were analyzed by flow cytometry using propidium iodide (PI) and Annexin V staining. Besides altering the pancreatic redox status, long-term CCK blockade inhibited the normal proliferation of acinar cells as indicated by the significant increase in G(0)/G(1)-phase cells and the decrease in G(2)/M-cells found in control rats treated with L364,718 for 7 days. A progressive depletion in pancreatic GSH was found from 3 to 24h after BPDO with similar values in L364,718-pretreated and non-treated rats, which led to a maximum peak in malondialdehyde (MDA) levels 6h after BPDO. However, plasma amylase activity and ascites volume indicated higher severity of AP in L364,718-pretreated rats. CCK blockade enhanced the alterations that appear in cell cycle distribution of acinar cells during AP demonstrated by the significantly higher increase in G(0)/G(1)-cells and decrease in S-cells found in L364,718-treated rats 48h after BPDO. Our results indicate that the renewal of acinar cells deleted by apoptosis 48h after BPDO worsens if CCK is blocked before inducing AP.
de la Mano
Ana M
AM
Department of Physiology and Pharmacology, University of Salamanca, 37008 Salamanca, Spain.
Sevillano
Sara
S
Manso
Manuel A
MA
de Dios
Isabel
I
D000208:Acute Disease; D000681:Amylases / Q000097:blood / Q000378:metabolism; D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D002453:Cell Cycle; D002455:Cell Division; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000502:physiology; D004396:Coloring Agents / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D020109:Devazepide / Q000494:pharmacology; D005434:Flow Cytometry; D016193:G1 Phase; D006727:Hormone Antagonists / Q000494:pharmacology; D010084:Oxidation-Reduction; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism*; D010195:Pancreatitis / Q000188:drug therapy / Q000378:metabolism*; D011419:Propidium / Q000494:pharmacology; D051381:Rats; D016192:Resting Phase, Cell Cycle; D013997:Time Factors
D017304:Annexin A5; D004396:Coloring Agents; D006727:Hormone Antagonists; D011419:Propidium; D004247:DNA; D002766:Cholecystokinin; D000681:Amylases; D020109:Devazepide