title: Effect of long-term CCK blockade on the pancreatic acinar cell renewal in rats with acute pancreatitis.
abstract: 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.
authors.affiliation: Department of Physiology and Pharmacology, University of Salamanca, 37008 Salamanca, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: de la Mano
authors.forename: Sara
authors.initials: S
authors.lastname: Sevillano
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Manso
authors.forename: Isabel
authors.initials: I
authors.lastname: de Dios
mesh_terms: 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
chemical_list: D017304:Annexin A5; D004396:Coloring Agents; D006727:Hormone Antagonists; D011419:Propidium; D004247:DNA; D002766:Cholecystokinin; D000681:Amylases; D020109:Devazepide