Ca2+ entry induced by cyclic ADP-ribose in intact T-lymphocytes.
Cyclic ADP-ribose (cADPr) is a potent Ca2+-mobilizing natural compound (Lee, H. C., Walseth, T. F., Bratt, G. T., Hayes, R. N., and Clapper, D. L. (1989) J. Biol. Chem. 264, 1608-1615) which has been shown to release Ca2+ from an intracellular store of permeabilized T-lymphocytes (Guse, A. H., Silva, C. P., Emmrich, F., Ashamu, G., Potter, B. V. L., and Mayr, G. W. (1995) J. Immunol. 155, 3353-3359). Microinjection of cADPr into intact single T lymphocytes dose dependently induced repetitive but irregular Ca2+ spikes which were almost completely dependent on the presence of extracellular Ca2+. The Ca2+ spikes induced by cADPr could be blocked either by co-injection of cADPr with the specific antagonist 8-NH2-cADPr, by omission of Ca2+ from the medium, or by superfusion of the cells with Zn2+ or SK-F 96365. Ratiometric digital Ca2+ imaging revealed that single Ca2+ spikes were initiated at several sites ("hot spots") close to the plasma membrane. These hot spots then rapidly formed a circular zone of high Ca2+ concentration below the plasma membrane which subsequently propagated like a closing optical diaphragm into the center of the cell. Taken together these data indicate a role for cADPr in Ca2+ entry in T-lymphocytes.
Guse
A H
AH
University of Hamburg, Institute of Physiological Chemistry, Department of Enzyme Chemistry, Grindelallee 117, D-20146 Hamburg, Germany. guse@uke.uni-hamburg.de
Berg
I
I
da Silva
C P
CP
Potter
B V
BV
Mayr
G W
GW
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D036563:Cyclic ADP-Ribose; D005456:Fluorescent Dyes; D016257:Fura-2; D006801:Humans; D019169:Jurkat Cells; D008845:Microinjections; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
D005456:Fluorescent Dyes; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D002118:Calcium; D016257:Fura-2