A Convenient Synthesis of 8-Alkyl-2' (or 3')-azido (or amino)-2' (or 3')-deoxyadenosine as Diverse Synthetic Precursors of Cyclic Adenosine Diphosphate Ribose (cADPR)

Abstract CD157, a glycosylphosphatidylinositol (GPI)–anchored protein encoded by a member of the CD38 NADase/ADP-ribosyl cyclase gene family, is expressed on the surface of most human circulating neutrophils. This work demonstrates that CD157 is a receptor that induces reorganization of the cytoskeleton and significant changes in cell shape, and that signals mediated by CD157 act through modulation of cytosolic Ca2+ concentration. These signals are independent of the products of CD157's enzymatic activities (ie, cyclic adenosine diphosphate [ADP]–ribose and ADP-ribose). Indeed, the enzymatic activities of CD157 in circulating neutrophils as well as in dimethyl sulfoxide (DMSO)–differentiated (CD157+/CD38-) HL-60 cells, are hardly detectable. This work also shows that the receptorial activity relies on cross-talk between CD157 and β2 integrin. CD157 localizes in GM1-enriched lipid rafts and, upon activation, it migrates to the uropod, a structure specialized in motility and adhesive functions. Indeed, CD157 is involved in adhesion to extracellular matrix proteins and in chemotaxis induced in vitro by formyl-methionyl-leucyl-phenylalanine (fMLP). These findings were consistent with the results obtained in neutrophils from patients with paroxysmal nocturnal hemoglobinuria (PNH), in which CD157 is deficient. These neutrophils showed constant defects in adhesion and migration. Our data attribute specific and crucial roles to CD157 in the regulation of innate immunity during inflammation.

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Characterization of Ca2+ release from heterogeneous Ca2+ stores in sarcoplasmic reticulum isolated from arterial and gastric smooth muscle

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y02-083 ◽

2002 ◽

Vol 80 (6) ◽

pp. 588-603 ◽

Cited By ~ 6

Author(s):

Marguerite A Stout ◽

Luc Raeymaekers ◽

Humbert De Smedt ◽

Rik Casteels

Keyword(s):

Smooth Muscle ◽

Sarcoplasmic Reticulum ◽

Slow Component ◽

Main Pulmonary Artery ◽

Adenosine Diphosphate ◽

Ruthenium Red ◽

Gastric Antrum ◽

Gastric Smooth Muscle ◽

Inositol 1,4,5 Trisphosphate ◽

Cyclic Adenosine Diphosphate

Ca2+ transport was investigated in vesicles of sarcoplasmic reticulum subfractionated from bovine main pulmonary artery and porcine gastric antrum using digitonin binding and zonal density gradient centrifugation. Gradient fractions recovered at 1533% sucrose were studied as the sarcoplasmic reticulum component using Fluo-3 fluorescence or 45Ca2+ Millipore filtration. Thapsigargin blocked active Ca2+ uptake and induced a slow Ca2+ release from actively loaded vesicles. Unidirectional 45Ca2+ efflux from passively loaded vesicles showed multicompartmental kinetics. The time course of an initial fast component could not be quantitatively measured with the sampling method. The slow release had a half-time of several minutes. Both components were inhibited by 20 μM ruthenium red and 10 mM Mg2+. Caffeine, inositol 1,4,5-trisphosphate, ATP, and diltiazem accelerated the slow component. A Ca2+ release component activated by ryanodine or cyclic adenosine diphosphate ribose was resolved with Fluo-3. Comparison of tissue responses showed that the fast Ca2+ release was significantly smaller and more sensitive to inhibition by Mg2+ and ruthenium red in arterial vesicles. They released more Ca2+ in response to inositol 1,4,5-trisphosphate and were more sensitive to activation by cyclic adenosine diphosphate ribose. Ryanodine and caffeine, in contrast, were more effective in gastric antrum. In each tissue, the fraction of the Ca+2 store released by sequential application of caffeine and inositol 1,4,5-trisphosphate depended on the order applied and was additive. The results indicate that sarcoplasmic reticulum purified from arterial and gastric smooth muscle represents vesicle subpopulations that retain functional Ca2+ channels that reflect tissue-specific pharmacological modulation. The relationship of these differences to physiological responses has not been determined.Key words: calcium channels, smooth muscle, sarcoplasmic reticulum.

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Functional relation between caffeine- and muscarine-sensitive Ca2+ stores and no Ca2+ releasing action of cyclic adenosine diphosphate-ribose in guinea-pig adrenal chromaffin cells

Neuroscience Letters ◽

10.1016/s0304-3940(02)00333-6 ◽

2002 ◽

Vol 326 (3) ◽

pp. 167-170 ◽

Cited By ~ 8

Author(s):

Toshio Ohta ◽

Arun R. Wakade ◽

Kazuki Yonekubo ◽

Shigeo Ito

Keyword(s):

Guinea Pig ◽

Chromaffin Cells ◽

Functional Relation ◽

Adenosine Diphosphate ◽

Adrenal Chromaffin Cells ◽

Adrenal Chromaffin ◽

Cyclic Adenosine Diphosphate

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Hypoxic pulmonary vasoconstriction: cyclic adenosine diphosphate-ribose, smooth muscle Ca2+ stores and the endothelium

Respiratory Physiology & Neurobiology ◽

10.1016/s1569-9048(02)00046-0 ◽

2002 ◽

Vol 132 (1) ◽

pp. 3-15 ◽

Cited By ~ 40

Author(s):

A.Mark Evans ◽

Michelle Dipp

Keyword(s):

Smooth Muscle ◽

Hypoxic Pulmonary Vasoconstriction ◽

Adenosine Diphosphate ◽

Pulmonary Vasoconstriction ◽

Cyclic Adenosine Diphosphate

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CD38/CD19: a lipid raft–dependent signaling complex in human B cells

Blood ◽

10.1182/blood-2006-12-061812 ◽

2007 ◽

Vol 109 (12) ◽

pp. 5390-5398 ◽

Cited By ~ 66

Author(s):

Silvia Deaglio ◽

Tiziana Vaisitti ◽

Richard Billington ◽

Luciana Bergui ◽

Paola Omede' ◽

...

Keyword(s):

B Cells ◽

B Lymphocytes ◽

Structural Organization ◽

Adenosine Diphosphate ◽

Surface Expression ◽

Signaling Complex ◽

The Third ◽

Human B Cells ◽

Lipid Microdomain ◽

Cyclic Adenosine Diphosphate

Abstract The present work deals with the mechanisms of signal transduction mediated via CD38 in normal and neoplastic human B lymphocytes. The results indicate that CD38 is a receptor and that CD38-mediated signals are tightly regulated at 3 distinct levels. The first concerns the structural organization of CD38, which is clearly divided into monomeric and dimeric forms. The second level of regulation is based on the dynamic localization of CD38 molecules in lipid microdomains within the plasma membrane. Lateral associations with other proteins, namely with the CD19/CD81 complex, determine the third level of control. Raft localization and association with the CD19 complex are prerequisites for CD38-mediated signals in tonsillar B cells and in continuous lines. Lastly, the results indicate that lipid microdomain disruption and silencing of CD19 directly impacts on CD38's ability to mediate Ca2+ fluxes, while leaving its surface expression unchanged. CD38 is also an enzyme capable of producing several calcium-mobilizing metabolites including cyclic adenosine diphosphate ribose (cADPR). Our inability to identify a correlation between the production of cADPR and the receptorial functions support the hypothesis that CD38 is a pleiotropic molecule whose behavior as a receptor is independent from its enzymatic activity.

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A Convenient and Versatile Synthesis of 2' (and 3')-Amino (and azido)-2' (and 3')-deoxyadenosine as Diverse Synthetic Precursors of Cyclic Adenosine Diphosphate Ribose (cADPR)

Bulletin of the Korean Chemical Society ◽

10.5012/bkcs.2004.25.2.243 ◽

2004 ◽

Vol 25 (2) ◽

pp. 243-248 ◽

Cited By ~ 5

Keyword(s):

Adenosine Diphosphate ◽

Cyclic Adenosine Diphosphate

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Antenatal betamethasone increases vascular reactivity to endothelin-1 by upregulation of CD38/cADPR signaling

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174413000512 ◽

2014 ◽

Vol 5 (1) ◽

pp. 56-62 ◽

Cited By ~ 6

Author(s):

J.-H. Lee ◽

J. Zhang ◽

G. A. Massmann ◽

J. P. Figueroa

Keyword(s):

Vascular Reactivity ◽

Adult Life ◽

Adenosine Diphosphate ◽

Adp Ribosyl Cyclase ◽

Antenatal Steroids ◽

Pregnant Sheep ◽

Antenatal Steroid ◽

Increased Sensitivity ◽

Cyclic Adenosine Diphosphate

Antenatal steroid administration is associated with hypertension in adult life; however, the mechanisms underlying this phenomenon are unclear. The aim of this study was to further characterize the effects of antenatal glucocorticoid exposure on the endothelin (ET-1) system, specifically to ascertain the role of the cyclic adenosine diphosphate ribose (cADPR)/ryanodine receptor pathway in the increased sensitivity to ET-1 observed in the offspring exposed to antenatal glucocorticoids. Pregnant sheep were randomly treated with betamethasone (Beta; 0.17 mg/kg) or vehicle at 80 and 81 days of gestation. In adults, we studied endothelium-denuded arterial segments of the brachial arteries. ET-1-induced vasoconstriction was significantly higher in the arteries from Beta sheep (F=3.5, P<0.05). Inhibition of ADP-ribosyl cyclase with 2-2'-dihydroxy-azobenzene significantly decreased the ET-1-induced contraction in Beta but not in vehicle-treated sheep. Nicotinamide attenuated ET-1 contraction in both, but it was significantly more pronounced in the Beta-treated sheep. No significant differences were observed following KCl-induced (6.25–75 mM) contraction. Nicotinamide (10 mM) significantly attenuated the KCl-induced vasoconstriction in both groups. In KCl (62.5 mM)-constricted arteries, the effect of nicotinamide (NIC) was significantly greater in the vehicle-treated sheep (50% relaxation v. 40% relaxation; t=2.2, P<0.05). In contrast, the sodium nitroprusside (SNP) relaxation was not statistically different. An additive effect was observed when NIC and SNP were used in combination and it was also more pronounced in vehicle-treated sheep. We conclude that the increased response to ET-1 is mediated by activation of the CD38/cADPR signaling pathway. Further studies are required to identify the effectors downstream from cADPR affected by exposure to antenatal steroids.

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