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

被引:13
作者
Cheng, HS [1 ]
So, SC [1 ]
Law, SH [1 ]
Chan, HC [1 ]
机构
[1] Chinese Univ Hong Kong, Fac Med, Dept Physiol, Shatin, Peoples R China
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 1999年 / 1449卷 / 03期
关键词
angiotensin II; AT(1) receptor; cAMP; Ca2+; CFPAC-1; cell;
D O I
10.1016/S0167-4889(99)00017-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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.
引用
收藏
页码:254 / 260
页数:7
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