CYCLOSPORINE-A INHIBITS PROTEIN-KINASE-C-MEDIATED AMYLASE RELEASE FROM ISOLATED RAT PANCREATIC ACINI

被引:6
作者
HOCKER, M
WASCHULEWSKI, IH
KERN, HF
DOMAGK, KA
SCHWARZHOFF, R
FOLSCH, UR
SCHMIDT, WE
机构
[1] CHRISTIAN ALBRECHTS UNIV KIEL,DEPT MED 1,MOLEC GASTROENTEROL LAB,D-24105 KIEL,GERMANY
[2] UNIV MARBURG,DEPT CELL BIOL & CELL PATHOL,W-3550 MARBURG,GERMANY
关键词
CYCLOSPORINE A; ISOLATED ACINI; ISOLATED LOBULES; AMYLASE RELEASE; INTRACELLULAR SIGNAL TRANSDUCTION; PROTEIN KINASE C;
D O I
10.1159/000201169
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The present study was performed to characterize a direct influence of cyclosporine A (CsA) on exocrine pancreatic enzyme secretion. CsA inhibited dose-dependently amylase release from isolated rat pancreatic acini in response to carbachoI or cholecystokinin octapeptide (CCK-8). A significant reduction in amylase release by 17% was observed at 0.2 mu mol/l CsA (p < 0.001) when compared to controls. At 0.2 mmol/l, CsA reduced amylase release in response to both secretagogues by maximally 45%, whereas basal secretion was not affected. CsA had no influence on CCK-8-stimulated increase in intracellular Ca2+ concentrations or amylase release in response to the Ca2+ ionophore A 23187. In contrast, the dose-response curve for amylase secretion induced by the phorbol ester phorbolmyristate-13-acetate was shifted to the right without a reduction of the maximal secretory response. Unexpectedly, vasoactive-intestinal-polypeptide- and secretin-stimulated acinar secretion was not diminished by CsA. In isolated pancreatic lobules exposed to 0.1 mmol/l CsA, amylase release stimulated by cerulein or veratridine was reduced by 26.7 +/- 2 or 28.3 +/- 4%, respectively. CsA had no influence on the displacement of I-125-Bolton-Hunter-labeled CCK-8 from acinar CCK receptors. The ultrastructure of cellular organelles in isolated lobules was not altered after incubation with 0.1 mmol/l CsA for 60 min. Our data suggested that CsA interferes with protein-kinase-C-mediated signal transduction in isolated rat pancreatic acini, without affecting cAMP-dependent signalling.
引用
收藏
页码:380 / 388
页数:9
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