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PMID: 14623867 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Spatio-temporal propagation of Ca2+ signals by cyclic ADP-ribose in 3T3 cells stimulated via purinergic P2Y receptors.

The Journal of cell biology ·Vol. 163 ·No. 4 ·2003-11-24 ·Pages 837-45

Bruzzone S, Kunerth S, Zocchi E, De Flora A, Guse AH

Abstract

The role of cyclic ADP-ribose in the amplification of subcellular and global Ca2+ signaling upon stimulation of P2Y purinergic receptors was studied in 3T3 fibroblasts. Either (1) 3T3 fibroblasts (CD38- cells), (2) 3T3 fibroblasts preloaded by incubation with extracellular cyclic ADP-ribose (cADPR), (3) 3T3 fibroblasts microinjected with ryanodine, or (4) 3T3 fibroblasts transfected to express the ADP-ribosyl cyclase CD38 (CD38+ cells) were used. Both preincubation with cADPR and CD38 expression resulted in comparable intracellular amounts of cyclic ADP-ribose (42.3 +/- 5.2 and 50.5 +/- 8.0 pmol/mg protein). P2Y receptor stimulation of CD38- cells yielded a small increase of intracellular Ca2+ concentration and a much higher Ca2+ signal in CD38-transfected cells, in cADPR-preloaded cells, or in cells microinjected with ryanodine. Confocal Ca2+ imaging revealed that stimulation of ryanodine receptors by cADPR or ryanodine amplified localized pacemaker Ca2+ signals with properties resembling Ca2+ quarks and triggered the propagation of such localized signals from the plasma membrane toward the internal environment, thereby initiating a global Ca2+ wave.

MeSH Terms
ADP-ribosyl Cyclase/deficiency,genetics ADP-ribosyl Cyclase 1 Animals Antigens, CD/genetics Calcium/metabolism Calcium Signaling/drug effects,physiology Cell Membrane/drug effects,metabolism Cyclic ADP-Ribose/genetics,metabolism,pharmacology Fibroblasts/drug effects,metabolism Membrane Glycoproteins Mice NIH 3T3 Cells Receptors, Purinergic P2/drug effects,metabolism Receptors, Purinergic P2Y1 Ryanodine/pharmacology Ryanodine Receptor Calcium Release Channel/drug effects,metabolism
Chemicals
Antigens, CD Membrane Glycoproteins P2ry1 protein, mouse Receptors, Purinergic P2 Receptors, Purinergic P2Y1 Ryanodine Receptor Calcium Release Channel Cyclic ADP-Ribose Ryanodine ADP-ribosyl Cyclase Cd38 protein, mouse ADP-ribosyl Cyclase 1 Calcium
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Bruzzone Santina
Department of Experimental Medicine, University of Genova, Italy.
Kunerth Svenja
Zocchi Elena
De Flora Antonio
Guse Andreas H
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200307016
Published
2003-11-24
Epub
2003-00-17
Pages
837-45
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2173669
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1083/jcb.200307016 PMC Full Text View journal details
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