Ectocellular CD38-catalyzed synthesis and intracellular Ca2+-signalling activity of cyclic ADP-ribose in T-lymphocytes are not functionally related.

Abstract:

:Cyclic ADP-ribose (cADPR) is a natural metabolite of beta-NAD+ with a potent Ca2+-mobilizing activity in different cell types, including T-lymphocytes. We investigated (i) whether stimulation of T-lymphocytes with different agonists affects the intracellular concentration of cADPR, and (ii) whether the lymphocyte antigen CD38, through its ectocellular ADP-ribosyl cyclase and cADPR-hydrolase enzymatic activities, can account for the regulation of the intracellular levels of cADPR and the Ca2+-mobilizing effects of this nucleotide in Jurkat and HPB.ALL T-lymphocytes. The anti-CD3 antibody OKT3, the sphingolipid sphingosine and lysophosphatidic acid induced an increase in intracellular cADPR with concomitant increases in the intracellular Ca2+ concentration ([Ca2+]i). In contrast, activation of an ectocellular ADP-ribosyl cyclase by preincubation of cells with beta-NAD+ led to a dose-dependent increase in cADPR, but no changes in [Ca2+]i were observed. However, extensive washing of the cells following preincubation with NAD+ demonstrated that the increases in cADPR were not intracellular but due to cell surface-associated nucleotide. Accordingly, measurements of ADP-ribosyl cyclase activity in intact T-cells showed ectocellular synthesis of cADPR, but no evidence was obtained for a shift of this activity into the cells which could account for intracellular accumulation of cADPR. Taken together, the results indicate no direct involvement of the ADP-ribosyl cyclase activity of CD38 on the regulation of the cADPR-mediated intracellular Ca2+-signalling in T-lymphocytes.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

da Silva CP,Schweitzer K,Heyer P,Malavasi F,Mayr GW,Guse AH

doi

10.1016/s0014-5793(98)01396-9

subject

Has Abstract

pub_date

1998-11-20 00:00:00

pages

291-6

issue

3

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(98)01396-9

journal_volume

439

pub_type

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