Angiotensin II-mediated signal transduction events in cystic fibrosis pancreatic duct cells
Publication in refereed journal



摘要Different signal transduction pathways, i.e. Ca2+- and cAMP-dependent, involved in mediating the effects of angiotensin II (AII) were investigated separately using the short-circuit current (I-sc) technique and radioimmunoassay (RIA) in a cystic fibrosis pancreatic cell line (CFPAC-1) which exhibits defective cAMP-dependent but intact Ca2+-dependent anion secretion. The AII-induced I-sc could be inhibited by the specific antagonist for AT(1), losartan (1 mu M), but not the antagonist for AT(2), PD123117 (up to 10 mu M). The AII-induced I-sc was also reduced by the treatment of the cells with a Ca2+ chelator, BAPTA-AM (100 mu M), indicating a dependence of the AII-induced anion secretion on the intracellular Ca2+. Treatment of the cells with pertussis toxin (0.1 mu g/ml) or a phospholipase C (PLC) inhibitor, U73122 (5 mu M), resulted in a substantial reduction in the AII-induced I-sc indicating involvement of Gi and PLC in the Ca2+-dependent anion secretion. RIA measurements showed that AII stimulated an increase in cAMP production which could be reduced by losartan, pertussis toxin and U73122 but not BAPTA-AM. In addition, inhibitors of cyclooxygenase, indomethacin (10 mu M) and piroxicam (10 mu M), did not have any effect on the AII-induced cAMP production, excluding the involvement of prostaglandins. Our results suggest that both AII-stimulated cAMP and Ca2+-dependent responses are mediated by the ATI receptor and Gi-coupled PLC pathway. However, the AII-stimulated cAMP production in CFPAC-1 cells is not dependent on Ca2+ or the formation of prostaglandins. (C) 1999 Elsevier Science B.V. All rights reserved.
著者Cheng HS, So SC, Law SH, Chan HC
期刊名稱Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
頁次254 - 260
關鍵詞angiotensin II; AT(1) receptor; Ca2+; cAMP; CFPAC-1 cell
Web of Science 學科類別Biochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Cell Biology; CELL BIOLOGY

上次更新時間 2020-14-09 於 03:08