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

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.