TAUROURSODEOXYCHOLIC ACID INHIBITS THE CYTOSOLIC CA++ INCREASE IN HUMAN NEUTROPHILS STIMULATED BY FORMYL-METHIONYL-LEUCYL-PHENYLALANINE

被引:20
作者
BEUERS, U [1 ]
THIEL, M [1 ]
BARDENHEUER, H [1 ]
PAUMGARTNER, G [1 ]
机构
[1] UNIV MUNICH, KLINIKUM GROSSHADERN, DEPT ANESTHESIOL, W-8000 MUNICH 70, GERMANY
关键词
D O I
10.1016/0006-291X(90)90800-3
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
The effect of the cytoprotective bile acid tauroursodeoxycholic acid (TUDCA) on basal cytosolic free Ca++ (Ca++)i and receptor-mediated (Ca++)i increase was studied in human polymorphonuclear neutrophils using the fluorescent dye quin2. Basal levels of (Ca++)i were 96 ± 6 nmol/1 (mean ± SEM, n=48). TUDCA and its cytotoxic epimer taurochenodeoxycholic acid (TCDCA) at 500 μmol/l increased (Ca++)i by 31 ± 12 and 27 ± 7 nmol/l, respectively (n=6, p<0.05). Stimulation of neutrophils with the chemotactic tripeptide N-formyl-methionyl-leucyl-phenylalanine (FMLP; 10-7 mol/l) induced a (Ca++)i increase of 200 ± 32 nmol/l which was inhibited after preincubation with TUDCA (500 μmol/l) or TUDCA-TCDCA (500 μmol/l, each) by 60.1% and 59.5%, respectively, but not with TCDCA (500 μmol/l) alone. The inhibitory effect of TUDCA on FMLP-induced (Ca++)i increase was strongly concentration-dependent and was nearly complete at 1000 μmol/l. Since (Ca++)i is discussed as a mediator of cellular injury we hypothesize that TUDCA may exert its protective effects at least partly via inhibition of (Ca++)i-mediated cytotoxic processes. © 1990.
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页码:1115 / 1121
页数:7
相关论文
共 18 条
[1]   HEPATOTOXIC BILE-ACIDS INCREASE CYTOSOLIC CA++ ACTIVITY OF ISOLATED RAT HEPATOCYTES [J].
ANWER, MS ;
ENGELKING, LR ;
NOLAN, K ;
SULLIVAN, D ;
ZIMNIAK, P ;
LESTER, R .
HEPATOLOGY, 1988, 8 (04) :887-891
[2]  
BOYUM A, 1968, SCAND J CLIN LAB INV, VS 21, P77
[3]   PROTECTIVE EFFECT OF INTRARENAL CALCIUM MEMBRANE BLOCKERS BEFORE OR AFTER RENAL ISCHEMIA - FUNCTIONAL, MORPHOLOGICAL, AND MITOCHONDRIAL STUDIES [J].
BURKE, TJ ;
ARNOLD, PE ;
GORDON, JA ;
BULGER, RE ;
DOBYAN, DC ;
SCHRIER, RW .
JOURNAL OF CLINICAL INVESTIGATION, 1984, 74 (05) :1830-1841
[4]   INTRACELLULAR CALCIUM HOMEOSTASIS [J].
CARAFOLI, E .
ANNUAL REVIEW OF BIOCHEMISTRY, 1987, 56 :395-433
[5]  
CHEUNG JY, 1986, NEW ENGL J MED, V314, P1670
[6]  
CHIEN KR, 1978, J BIOL CHEM, V253, P4809
[7]  
COMBETTES L, 1989, J BIOL CHEM, V264, P157
[8]   RELEASE OF CA-2+ FROM THE ENDOPLASMIC-RETICULUM IS NOT THE MECHANISM FOR BILE-ACID INDUCED CHOLESTASIS AND HEPATOTOXICITY IN THE INTACT RAT-LIVER [J].
FARRELL, GC ;
DUDDY, SK ;
KASS, GEN ;
LLOPIS, J ;
GAHM, A ;
ORRENIUS, S .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 85 (04) :1255-1259
[9]  
GLEESON D, 1990, J LIPID RES, V31, P781
[10]  
HEUMAN DM, 1989, J LIPID RES, V30, P719