Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 16905135

Bradykinin activates ADP-ribosyl cyclase in neuroblastoma cells: intracellular concentration decrease in NAD and increase in cyclic ADP-ribose.

Haruhiro Higashida·Alla Salmina·Minako Hashii·Shigeru Yokoyama·Jia-Sheng Zhang·Mami Noda·Zen-Guo Zhong·Duo Jin
View original source ↗Export metadata ↓

Abstract

ADP-ribosyl cyclase activity in the crude membrane fraction of neuroblastomaxglioma NGPM1-27 hybrid cells was measured by monitoring [(3)H] cyclic ADP-ribose (cADPR) formation from [(3)H] NAD(+). Bradykinin (BK) at 100nM increased ADP-ribosyl cyclase activity by about 2.5-fold. Application of 300nM BK to living NGPM1-27 cells decreased NAD(+) to 78% of the prestimulation level at 30s. In contrast, intracellular cADPR concentrations were increased by 2-3-fold during the period from 30 to 120s after the same treatment. Our results suggest that cADPR is one of the second messengers downstream of B(2) BK receptors.

Explore related subjects

ADP-ribosyl CyclaseAnimalsBradykininCell Line, TumorCell MembraneCyclic ADP-RiboseHybrid CellsMiceNADNeuroblastomaRatsSecond Messenger SystemsVasodilator AgentsJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Haruhiro Higashida, Alla Salmina, Minako Hashii, Shigeru Yokoyama, Jia-Sheng Zhang, Mami Noda, Zen-Guo Zhong, Duo Jin. 2006-08-08. Bradykinin activates ADP-ribosyl cyclase in neuroblastoma cells: intracellular concentration decrease in NAD and increase in cyclic ADP-ribose.. https://doi.org/10.1016/j.febslet.2006.07.084

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Identification and functional characterization of the hepatic stellate cell CD38 cell surface molecule.

The activation of hepatic stellate cells (HSCs) is a critical event in hepatic fibrosis, because these cells are the main producers of extracellular matrix proteins in the liver and contribute to the modulation of inflammatory responses via the secretion of several cytokines and the expression of adhesion molecules. The goal of the present study was to characterize cell surface proteins that regulate HSC activation. To this end, a panel of monoclonal antibodies (mAbs) was generated. mAb 14.27 recognized a protein of 45 kd that was highly expressed on HSCs. Affinity purification of this protein followed by sequencing revealed that protein to be CD38. We subsequently demonstrated that CD38 was constitutively expressed by HSCs and that its expression increased after in vitro and in vivo activation. mAb 14.27 induced an increase in cytosolic Ca2+ levels in HSCs, showing that it functions as an agonistic antibody. Moreover, the effects mediated by the CD38 mAb included induction of the proinflammatory cytokine interleukin-6 and up-regulation of the adhesion molecules intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and neural cell adhesion molecule. Collectively, our data suggest that CD38 can act as a regulator of HSC activation and effector functions.

ADP-ribosyl Cyclase↗
PubMed2006

Discovery of a small-molecule inhibitor for kidney ADP-ribosyl cyclase: Implication for intracellular calcium signal mediated by cyclic ADP-ribose.

ADP-ribosyl cyclase (ADPR-cyclase) produces a Ca2+-mobilizing second messenger, cyclic ADP- ribose (cADPR), from beta-NAD+. A prototype of mammalian ADPR-cyclases is a lymphocyte antigen CD38. Accumulating evidence indicates that ADPR-cyclases other than CD38 are expressed in various cells and organs. In this study, we discovered a small molecule inhibitor of kidney ADPR-cyclase. This compound inhibited kidney ADPR-cyclase activity but not CD38, spleen, heart or brain ADPR-cyclase activity in vitro. Characterization of the compound in a cell-based system revealed that an extracellular calcium-sensing receptor (CaSR)- mediated cADPR production and a later long-lasting increase in intracellular Ca2+ concentration ([Ca2+]i) in mouse mesangial cells were inhibited by the pre-treatment with this compound. In contrast, the compound did not block CD3/TCR-induced cADPR production and the increase of [Ca2+]i in Jurkat T cells, which express CD38 exclusively. The long-lasting Ca2+ signal generated by both receptors was inhibited by pre-treatment with an antagonistic cADPR derivative, 8-Br-cADPR, indicating that the Ca2+ signal is mediated by the ADPR-cyclase metabolite, cADPR. Moreover, among structurally similar compounds tested, the compound inhibited most potently the cADPR production and Ca2+ signal induced by CaSR. These findings provide evidence for existence of a distinct ADPR-cyclase in the kidney and basis for the development of tissue specific inhibitors.

ADP-ribosyl Cyclase↗
PubMed2006

Overexpression of human CD38/ADP-ribosyl cyclase enhances acetylcholine-induced Ca2+ signalling in rodent NG108-15 neuroblastoma cells.

The role of cyclic ADP-ribose (cADPR) and its synthetic enzyme, CD38, as a downstream signal of muscarinic acetylcholine receptors (mAChRs) was examined in neuroblastoma cells expressing M1 mAChRs (NGM1). NGM1 cells were further transformed with both wild-type and mutant (C119K/C201E) human CD38. The dual transformed cells exhibited higher cADPR formation than ADPR production and elevated intracellular free Ca(2+) concentrations ([Ca(2+)](i)) in response to ACh. These phenotypes were analyzed in detail in a representative CD38 clone. The intracellular cADPR concentration by ACh application was significantly increased by CD38 overexpression. Digital image analysis by a confocal microscopy revealed that topographical distribution of the sites of Ca(2+) release was unchanged between control and overexpressed cells. These results indicate that cADPR is an intracellular messenger of Ca(2+) signalling, suggesting that CD38 can contribute to mAChR-cADPR signalling.

ADP-ribosyl Cyclase↗