ADP-ribosyl cyclase and GDP-ribosyl cyclase activities are not always equivalent: Impact on the study of the physiological role of cyclic ADP-ribose

2005 ◽  
Vol 346 (2) ◽  
pp. 336-338 ◽  
Author(s):  
Frances E. Lund ◽  
Marie-Jo Moutin ◽  
Hélène Muller-Steffner ◽  
Francis Schuber
Keyword(s):  
Physiological Role ◽  
Adp Ribosyl Cyclase ◽  
Cyclic Adp Ribose

Intracellular ADP-ribose inhibits ATP-sensitive K+ channels in rat ventricular myocytes

1996 ◽  
Vol 271 (2) ◽  
pp. C464-C468 ◽  
Author(s):  
Y. G. Kwak ◽  
S. K. Park ◽  
U. H. Kim ◽  
M. K. Han ◽  
J. S. Eun ◽  
...  
Keyword(s):  
Single Channel ◽  
Ventricular Myocytes ◽  
Physiological Role ◽  
Hill Coefficient ◽  
K Channel ◽  
Channel Activity ◽  
Rat Ventricular Myocytes ◽  
Cyclic Adp Ribose ◽  
The Hill

Cyclic ADP-ribose (cADPR), an NAD metabolite, has been shown to be a messenger for Ca2+ mobilization from intracellular Ca2+ stores. However, the physiological role of ADP-ribose (ADPR), another metabolite of NAD, is not known. We examined the effects of cADPR and ADPR on the ATP-sensitive K+ channel (KATP) activity in rat ventricular myocytes by use of the inside-out patch-clamp configuration. ADPR, but not cADPR, inhibited the channel activity at micromolar range with an inhibitor constant (Ki) of 38.4 microM. The Hill coefficient was 0.9. ATP inhibited the K+ channel with a Ki of 77.8 microM, and the Hill coefficient was 1.8. Single-channel conductance was not affected by ADPR. These findings strongly suggest that ADPR may act as a regulator of KATP channel activity.

scholarly journals Renal vasoconstriction by vasopressin V1a receptors is modulated by nitric oxide, prostanoids, and superoxide but not the ADP ribosyl cyclase CD38

2014 ◽  
Vol 306 (10) ◽  
pp. F1143-F1154 ◽  
Author(s):  
Nicholas G. Moss ◽  
Tayler E. Kopple ◽  
William J. Arendshorst
Keyword(s):  
Nitric Oxide ◽  
Contractile Response ◽  
Receptor Activation ◽  
Wild Type ◽  
Renal Vasoconstriction ◽  
Adp Ribosyl Cyclase ◽  
Cyclic Adp Ribose ◽  
Renal Vascular ◽  
Dose Dependent

Renal blood flow (RBF) responses to arginine vasopressin (AVP) were tested in anesthetized wild-type (WT) and CD38−/− mice that lack the major calcium-mobilizing second messenger cyclic ADP ribose. AVP (3–25 ng) injected intravenously produced dose-dependent decreases in RBF, reaching a maximum of 25 ± 2% below basal RBF in WT and 27 ± 2% in CD38−/− mice with 25 ng of AVP. Renal vascular resistance (RVR) increased 75 ± 6% and 78 ± 6% in WT and CD38−/− mice. Inhibition of nitric oxide (NO) synthase with nitro-l-arginine methyl ester (l-NAME) increased the maximum RVR response to AVP to 308 ± 76% in WT and 388 ± 81% in CD38−/− ( P < 0.001 for both). Cyclooxygenase inhibition with indomethacin increased the maximum RVR response to 125 ± 15% in WT and 120 ± 14% in CD38−/− mice ( P < 0.001, <0.05). Superoxide suppression with tempol inhibited the maximum RVR response to AVP by 38% in both strains ( P < 0.005) but was ineffective when administered after l-NAME. The rate of RBF recovery (relaxation) after AVP was slowed by l-NAME and indomethacin ( P < 0.001, <0.005) but was unchanged by tempol. All vascular responses to AVP were abolished by an AVP V1a receptor antagonist. A V2 receptor agonist or antagonist had no effect on AVP-induced renal vasoconstriction. Taken together, the results indicate that renal vasoconstriction by AVP in the mouse is strongly buffered by vasodilatory actions of NO and prostanoids. The vasoconstriction depends on V1a receptor activation without involvement of CD38 or concomitant vasodilatation by V2 receptors. The role of superoxide is to enhance the contractile response to AVP, most likely by reducing the availability of NO rather than directly stimulating intracellular contraction signaling pathways.

Catalytic properties of the retinal rod outer segment disk ADP-ribosyl cyclase

2011 ◽  
Vol 28 (2) ◽  
pp. 121-128 ◽  
Author(s):  
ANDREA FABIANO ◽  
ISABELLA PANFOLI ◽  
DANIELA CALZIA ◽  
MAURIZIO BRUSCHI ◽  
SILVIA RAVERA ◽  
...  
Keyword(s):  
Divalent Cations ◽  
Cyclase Activity ◽  
The Novel ◽  
Intracellular Membrane ◽  
Adp Ribosyl Cyclase ◽  
Retinal Rod ◽  
Cyclic Adp Ribose ◽  
Response To Change ◽  
Shed Light

AbstractCyclic ADP-ribose (cADPR) is a second messenger modulating intracellular calcium levels. We have previously described a cADPR-dependent calcium signaling pathway in bovine rod outer segments (ROS), where calcium ions play a pivotal role. ROS ADP-ribosyl cyclase (ADPR-cyclase) was localized in the membrane fraction. In the present work, we examined the properties of the disk ADPR-cyclase through the production of cyclic GDP-ribose from the NAD+ analogue NGD+. The enzyme displayed an estimated Km for NGD+ of 12.5 ± 0.3 μM, a Vmax of 26.50 ± 0.70 pmol cyclic GDP-ribose synthesized/min/mg, and optimal pH of 6.5. The effect of divalent cations (Zn2+, Cu2+, and Ca2+) was also tested. Micromolar Zn2+ and Cu2+ inhibited the disk ADPR-cyclase activity (half maximal inhibitory concentration, IC50 = 1.1 and 3.6 μM, respectively). By contrast, Ca2+ ions had no effect. Interestingly, the properties of the intracellular membrane–associated ROS disk ADPR-cyclase are more similar to those of the ADPR-cyclase found in CD38-deficient mouse brain, than to those of CD38 or CD157. The novel intracellular mammalian ADPR-cyclase would elicit Ca2+ release from the disks at various rates in response to change in free Ca2+ concentrations, caused by light versus dark adaptation, in fact there was no difference in disk ADPR-cyclase activity in light or dark conditions. Data suggest that disk ADPR-cyclase may be a potential target of retinal toxicity of Zn2+ and may shed light to the role of Cu2+ and Zn2+ deficiency in retina.

scholarly journals Cyclic ADP-ribose is a second messenger in the lipopolysaccharide-stimulated proliferation of human peripheral blood mononuclear cells

2003 ◽  
Vol 375 (2) ◽  
pp. 395-403 ◽  
Author(s):  
Santina BRUZZONE ◽  
Antonio DE FLORA ◽  
Cesare USAI ◽  
Richard GRAEFF ◽  
Hon Cheung LEE
Keyword(s):  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Second Messenger ◽  
Immune Recognition ◽  
Adp Ribosyl Cyclase ◽  
T Lymphocyte Proliferation ◽  
Cyclic Adp Ribose ◽  
Membrane Bound

Cyclic ADP-ribose (cADPR), a universal calcium mobilizer from intracellular stores, was recently demonstrated to stimulate proliferation of various cell types. The role of cADPR in a specific process of monocyte- and plasma-mediated activation of T-lymphocytes by lipopolysaccharide (LPS) was addressed using human mononuclear cells from peripheral blood (PBMCs). Incubation of PBMCs with 0.1 μg/ml of LPS for 24 h provided a doubling in the intracellular levels of cADPR as compared with unstimulated PBMCs. The cADPR increase was abolished either by prior removal of monocytes or by pre-incubating a whole PBMC population with a monoclonal antibody against the monocyte marker CD14. The increased concentrations of intracellular cADPR elicited by LPS stimulation were paralleled by significant increases in NAD+ levels and in the activities of ectocellular and membrane-bound fractions of ADP-ribosyl cyclase/cADPR hydrolase activities. A cytosolic ADP-ribosyl cyclase was also detectable in PBMCs and its activity was comparably enhanced by LPS stimulation. This soluble cyclase is distinguished from the membrane-bound cyclase by both substrate and inhibitor sensitivities. LPS-stimulated PBMCs showed 2–3-fold increases of intracellular calcium ([Ca2+]i), and these changes were prevented completely by the cADPR antagonist 8-Br-cADPR and by ryanodine. Both compounds, and the cyclase inhibitor nicotinamide, significantly inhibited the T-lymphocyte proliferation induced by LPS in PBMCs. These results demonstrate that cADPR plays a role of second messenger in the adaptive immune recognition process of LPS-stimulated proliferation of PBMCs.

scholarly journals Regulatory Role of CD38 (ADP-ribosyl Cyclase/Cyclic ADP-ribose Hydrolase) in Insulin Secretion by Glucose in Pancreatic βCells

1995 ◽  
Vol 270 (50) ◽  
pp. 30045-30050 ◽  
Author(s):  
Ichiro Kato ◽  
Shin Takasawa ◽  
Atsuya Akabane ◽  
Osamu Tanaka ◽  
Hiroshi Abe ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Regulatory Role ◽  
Adp Ribosyl Cyclase ◽  
Cyclic Adp Ribose

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

2003 ◽  
Vol 163 (4) ◽  
pp. 837-845 ◽  
Author(s):  
Santina Bruzzone ◽  
Svenja Kunerth ◽  
Elena Zocchi ◽  
Antonio De Flora ◽  
Andreas H. Guse
Keyword(s):  
Ryanodine Receptors ◽  
P2y Receptors ◽  
3T3 Cells ◽  
Cd38 Expression ◽  
3T3 Fibroblasts ◽  
Adp Ribosyl Cyclase ◽  
Cyclic Adp Ribose ◽  
Spatio Temporal ◽  
Stimulation Of

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.

scholarly journals Ca2+-induced Ca2+ Release in Chromaffin Cells Seen from inside the ER with Targeted Aequorin

1999 ◽  
Vol 144 (2) ◽  
pp. 241-254 ◽  
Author(s):  
Maria Teresa Alonso ◽  
Maria José Barrero ◽  
Pedro Michelena ◽  
Estela Carnicero ◽  
Inmaculada Cuchillo ◽  
...  
Keyword(s):  
Chromaffin Cells ◽  
Physiological Role ◽  
Dependent Manner ◽  
Excitable Cells ◽  
Permeabilized Cells ◽  
Low Concentrations ◽  
Cyclic Adp Ribose ◽  
Cell Depolarization ◽  
Adrenal Chromaffin

The presence and physiological role of Ca2+-induced Ca2+ release (CICR) in nonmuscle excitable cells has been investigated only indirectly through measurements of cytosolic [Ca2+] ([Ca2+]c). Using targeted aequorin, we have directly monitored [Ca2+] changes inside the ER ([Ca2+]ER) in bovine adrenal chromaffin cells. Ca2+ entry induced by cell depolarization triggered a transient Ca2+ release from the ER that was highly dependent on [Ca2+]ER and sensitized by low concentrations of caffeine. Caffeine-induced Ca2+ release was quantal in nature due to modulation by [Ca2+]ER. Whereas caffeine released essentially all the Ca2+ from the ER, inositol 1,4,5-trisphosphate (InsP3)- producing agonists released only 60–80%. Both InsP3 and caffeine emptied completely the ER in digitonin-permeabilized cells whereas cyclic ADP-ribose had no effect. Ryanodine induced permanent emptying of the Ca2+ stores in a use-dependent manner after activation by caffeine. Fast confocal [Ca2+]c measurements showed that the wave of [Ca2+]c induced by 100-ms depolarizing pulses in voltage-clamped cells was delayed and reduced in intensity in ryanodine-treated cells. Our results indicate that the ER of chromaffin cells behaves mostly as a single homogeneous thapsigargin-sensitive Ca2+ pool that can release Ca2+ both via InsP3 receptors or CICR.

Nitric oxide inhibits ADP-ribosyl cyclase through a cGMP-independent pathway in airway smooth muscle

2002 ◽  
Vol 283 (5) ◽  
pp. L1065-L1071 ◽  
Author(s):  
Thomas A. White ◽  
Timothy F. Walseth ◽  
Mathur S. Kannan
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Hydrolase Activity ◽  
Adp Ribosyl Cyclase ◽  
Cyclic Adp Ribose ◽  
Protein Sulfhydryl ◽  
Intracellular Ca ◽  
Protein Sulfhydryl Groups

There is evidence for a role of cyclic ADP-ribose (cADPR) in intracellular Ca2+ regulation in smooth muscle. cADPR is synthesized and degraded by ADP-ribosyl cyclase and cADPR hydrolase, respectively, by a bifunctional protein, CD38. Nitric oxide (NO) inhibits intracellular Ca2+mobilization in airway smooth muscle. The present study was designed to determine whether this inhibition is due to regulation of ADP-ribosyl cyclase and/or cADPR hydrolase activity. Sodium nitroprusside (SNP) and S-nitroso- N-acetylpenicillamine, NO donors, produced a concentration-dependent decrease in ADP-ribosyl cyclase, but not cADPR hydrolase, activity. The NO scavenger carboxy-PTIO prevented and reversed, and reduced glutathione prevented, the inhibition of ADP-ribosyl cyclase by SNP, suggesting S-nitrosylation by NO as a mechanism. N-ethylmaleimide, which covalently modifies protein sulfhydryl groups, making them incapable of nitrosylation, produced a marked inhibition of ADP-ribosyl cyclase, but not cADPR hydrolase, activity. SNP and N-ethylmaleimide significantly inhibited the ADP-ribosyl cyclase activity in recombinant human CD38 without affecting the cADPR hydrolase activity. These results provide a novel mechanism for differential regulation of CD38 by NO through a cGMP-independent pathway involving S-nitrosylation of thiols.

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