Influence of aprotinin and promazine on survival of isolated pancreatic acinar cells.
Aprotinin, a protease inhibitor, and promazine, an inhibitor of phospholipase A2, were tested for possible inhibition of pancreatic acinar cell (PAC) decline induced by uncoupling of oxidative phosphorylation with 2,4-dinitrophenol (DNP) or by temporary anoxia/reoxygenation. In incubates of acinar cells isolated from rat pancreas the presence of aprotinin did not influence the survival of cells treated with these noxae. This finding excludes that extracellulary acting trypsin, possibly released from damaged cells, contributes to further cell death. While promazine at concentrations of 15 to 20 nmol.(10(6) cells)-1 was well tolerated by untreated PAC, higher concentrations caused a clear reduction of cell viability. At optimum concentration promazine was without influence on DNP-treated cells, but it had a beneficial effect on survival and morphology of anoxia-treated PAC (p less than or equal to 0.05). Therefore, it can be assumed that after anoxia/reoxygenation the membrane phospholipase A2 becomes stimulated and causes phospholipid depletion with final death of the cells. It is suggested that such a mechanism may contribute to the initial cell damage in the pathogenesis of acute pancreatitis, too.
Letko
G
G
Division of Experimental Surgery, Medical Academy of Magdeburg, Germany.
Falkenberg
B
B
D000208:Acute Disease; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects*; D005260:Female; D066298:In Vitro Techniques; D010179:Pancreas / Q000166:cytology* / Q000187:drug effects; D010195:Pancreatitis / Q000209:etiology / Q000473:pathology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D054467:Phospholipases A2; D011395:Promazine / Q000494:pharmacology*; D051381:Rats; D013194:Staining and Labeling; D014343:Trypan Blue
D007611:Aprotinin; D010741:Phospholipases A; D054467:Phospholipases A2; D014343:Trypan Blue; D011395:Promazine