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/l (mean +/- SEM, n = 48). TUDCA and its cytotoxic epimer taurochenodeoxycholic acid (TCDCA) at 500 mumols/l increased (Ca++)i by 31 +/- 12 and 27 +/- 7 nmol/l, respectively (n = 6, p less than 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 mumols/l) or TUDCA + TCDCA (500 mumols/l, each) by 60.1% and 59.5%, respectively, but not with TCDCA (500 mumols/l) alone. The inhibitory effect of TUDCA on FMLP-induced (Ca++)i increase was strongly concentration-dependent and was nearly complete at 1000 mumols/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.
Beuers
U
U
Department of Medicine II, University of Munich, F.R.G.
Thiel
M
M
Bardenheuer
H
H
Paumgartner
G
G
D002118:Calcium / Q000097:blood*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007536:Isomerism; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*
D013655:Taurochenodeoxycholic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; C031655:ursodoxicoltaurine; D002118:Calcium