Abstract

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.

Highlights

  • Intracellular Ca2ϩ signaling is one of the major events transducing extracellular signals into many different types of living cells

  • In Jurkat T-lymphocytes it is well accepted that D-myoinositol 1,4,5-trisphosphate (IP3)1 releases Ca2ϩ from an intracellular store located in the endoplasmic reticulum via its specific receptor [1,2,3]

  • The trigger to switch on the capacitative Ca2ϩ entry has been reported to be likely the depletion of the IP3-sensitive intracellular Ca2ϩ pool in T cells (4 – 6)

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Summary

Introduction

Intracellular Ca2ϩ signaling is one of the major events transducing extracellular signals into many different types of living cells. We and others have recently demonstrated cADPr-induced Ca2ϩ release from a non-thapsigargin sensitive intracellular store of T-lymphocyte cell lines [16, 17].

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