Modulation of store-operated ca2+ entry by cyclic-ADP-ribose

M. Thompson, T. White, Eduardo N. Chini

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Store-operated Ca2+ entry plays an important role in Ca2+ homeostasis in cells but the mechanisms of control of these channels are not completely understood. We describe an investigation of the role of the CD38-cyclic-ADP-ribose (cADPR)-ryanodine-channel (RyR) signaling pathway in store-operated Ca2+ entry in human smooth muscle. We observed that human myometrial cells have a functional store-operated Ca2+ entry mechanism. Furthermore, we observed the presence of transient receptor potential 1, 3, 4, 5, and 6 ion channels in human myometrial cells. Store-operated Ca2+ transient was inhibited by at least 50-70% by several inhibitors of the RyR, including ryanodine (10 μM), dantrolene (10 μM), and ruthenium red (10 μM). Furthermore, the cell permeable inhibitor of the cADPR-system, 8Br-cADPR (100 μM), is a potent inhibitor of the store-operated entry, decreasing the store operated entry by 80%. Pre-incubation of cells with 100 μM cADPR and the hydrolysis-resistant cADPR analog 3-deaza-cADPR (50 μM), but not with ADP-ribose (ADPR) leads to a 1.6-fold increase in the store-operated Ca2+ transient. In addition, we observed that nicotinamide (1-10 mM), an inhibitor of cADPR synthesis, also leads to inhibition of the store-operated Ca2+ transient by 50-80%. Finally, we observed that the transient receptor potential channels, RyR, and CD38 can be co-immunoprecipitated, indicating that they interact in vivo. Our observations clearly implicate the CD38-cADPR-ryanodine signaling pathway in the regulation of store-operated Ca2+ entry in human smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)739-748
Number of pages10
JournalBrazilian Journal of Medical and Biological Research
Volume39
Issue number6
DOIs
StatePublished - Jun 1 2006

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Keywords

  • Calcium entry
  • Cyclic-ADP-ribose
  • Endoplasmic reticulum
  • Human smooth muscle
  • IP3
  • Ryanodine channel

ASJC Scopus subject areas

  • Biophysics
  • Neuroscience(all)
  • Biochemistry
  • Physiology
  • Immunology
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Cell Biology

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