ライフサイエンスコーパス: cADPR

1 cADPR also controls intracellular calcium release in the

2 cADPR can induce intracellular calcium release in an ino

3 cADPR had no significant impact on activity of single ca

4 cADPR is an endogenous calcium-mobilizing agent that in

5 cADPR modulates the circadian oscillator's transcription

6 -dependent pathways with heparin and 8-NH(2)-cADPR was required to block the mGluR-induced Ca(2+) rel

7 and there was no further attenuation by 8Br-cADPR.

8 ermeant cADPR antagonist, 8-bromo-cADPR (8Br-cADPR), on the [Ca2+]i responses to ACh, histamine and e

9 e cADP receptor inhibitor 8-bromo-cADPR (8Br-cADPR).

10 In cells preincubated with 100 microM 8Br-cADPR, the [Ca2+]i responses to ACh and ET-1 were signif

11 The effects of 8Br-cADPR were concentration dependent.

12 but not affected by U73122 [GenBank] or 8Br-cADPR.

13 In support of this notion, a cADPR antagonist abolished the NO-induced potentiation o

14 We found that a cADPR antagonist and a CD38 substrate analogue inhibited

15 alcium-release second messenger cyclic ADPR (cADPR), has no defined role as an intracellular signalli

16 inamide, ADP-ribose (ADPR), and cyclic ADPR (cADPR).

17 Although cADPR and NAADP are structurally and functionally differ

18 syntheses of established antagonists 8-amino-cADPR 2 and 8-bromo-cADPR 3.

19 re partially inhibited by heparin or 8-amino-cADPR alone, but eliminated by the presence of both, ind

20 th muscle, and the cADPR antagonist, 8-amino-cADPR, abolishes [Ca2+]i oscillations elicited by acetyl

21 HEPES buffer, with heat-inactivated 8-amino-cADPR, or in cells pretreated with ryanodine (2 microM)

22 s of either cADPR or its antagonist, 8-amino-cADPR, was ineffective in altering normal CICR in myocyt

23 investigated this possibility using 8-amino-cADPR, which has been found to antagonize the Ca2+-relea

24 lum function before injection of the 8-amino-cADPR.

25 Thapsigargin completely blocks IP(3) and cADPR responses and decreases but does not prevent the r

26 Simultaneous inhibition of both IP(3)- and cADPR-dependent pathways with heparin and 8-NH(2)-cADPR

27 in an increase in ADPR cyclase activity and cADPR levels, as well as elevated expression of ABA-resp

28 TRPM2 as a coincidence detector for ADPR and cADPR signaling and provide a functional context for cAD

29 Both 2'-P-cADPR and cADPR appear to act by a similar mechanism based on simi

30 s using pharmacologic inhibitors of CD38 and cADPR as well as mice deficient in Cd38 (Cd38(-/-)).

31 gh chemokine receptors that rely on CD38 and cADPR for activity, including mouse FPR1, CXCR4, and CCR

32 this study, we examined the role of CD38 and cADPR in acinar cell Ca(2+) signals and acinar injury du

33 We also show that CD38 and cADPR modulate calcium mobilization in chemokine-stimula

34 ctional enzymes with ADP-ribosyl cyclase and cADPR hydrolase activity.

35 in response to the second messengers IP3 and cADPR (ER) or NAADP (acidic organelles).

36 Thapsigargin completely blocked IP3 and cADPR responses as well as NAADP-induced Ca2+ oscillatio

37 ion of both inositol trisphosphate (IP3) and cADPR evoke repetitive Ca2+ spiking [6], the cADPR antag

38 , indicating a requirement for both IP3- and cADPR-dependent Ca2+ release.

39 observations support generation of NAADP and cADPR by intracellular CD38, which contributes to effect

40 esting the possible involvement of NAADP and cADPR in neurotransmitter-elicited intracellular Ca2+ re

41 amily, catalyzes synthesis of both NAADP and cADPR in vitro However, it remains unclear whether this

42 c acinar cells have indicated that NAADP and cADPR receptors are essential for Ca2+ release.

43 t CD38(-/-) mouse hearts supported NAADP and cADPR synthesis.

44 or, their enzymatic functions toward NAD and cADPR homeostasis have evolved divergently.

45 m deprivation, ABA stimulates, in a PKA- and cADPR-dependent fashion, the mitogen-activated kinase ER

46 ) in Arabidopsis (Arabidopsis thaliana), and cADPR has been proposed to play a central role in signal

47 In animals, cADPR targets the ryanodine receptor present in the sarc

48 y important roles in signal transduction, as cADPR regulates calcium release from intracellular store

49 DPR antagonist 8-NH2-cADPR [7], which blocks cADPR-evoked but not IP3-evoked Ca2+ spiking, can abolis

50 Both cADPR and ADPR are calcium messengers that can mobilize

51 N1-cIDPR 2, 6-thio N1-cIDPR antagonizes both cADPR- and N1-cIDPR-induced Ca(2+) release but possesses

52 inamide (20 mM) or the cADPR antagonist 8-Br-cADPR (30 muM) abrogated TLCS-induced Ca(2+) signals and

53 of TRPM2, whereas the cADPR antagonist 8-Br-cADPR exhibits the reverse block specificity.

54 clic adenosine diphosphoribosyl ribose (8-Br-cADPR), an antagonist of cADPR.

55 TGF-beta1, whereas the cADPR antagonist 8-Br-cADPR, Ca(2+) chelation, and antagonism of L-type Ca(2+)

56 sts and can be completely suppressed by 8-Br-cADPR, which suggests that cADPR and NAADP share a commo

57 membrane-permeant cADPR antagonist, 8-bromo-cADPR (8Br-cADPR), on the [Ca2+]i responses to ACh, hist

58 k] or by the cADP receptor inhibitor 8-bromo-cADPR (8Br-cADPR).

59 shed antagonists 8-amino-cADPR 2 and 8-bromo-cADPR 3.

60 The cADPR antagonist 8-bromo-cADPR attenuated the Ca2+ responses to the agonists in c

61 Most importantly, we showed that 8-bromo-cADPR blocks HPV induced by alveolar hypoxia in the vent

62 membrane-permeant cADPR antagonist, 8-bromo-cADPR, blocked sustained HPV by blocking Ca(2+) release

63 P is potentiated by IP(3) but antagonized by cADPR.

64 tion of cADPR to ADP-ribose was catalyzed by cADPR hydrolase, which was found to be predominantly ass

65 opsis are similarly up- and downregulated by cADPR and contributed to the identification of new ABA-r

66 ated rats, the rate of cADPR inactivation by cADPR hydrolase and the activity of NADase was increased

67 that HPV is both triggered and maintained by cADPR in the rat lung in situ.

68 expression in target cells, are mediated by cADPR-Ca2+ release pathway.

69 f the chemoattractant receptors regulated by cADPR bind to ligands that are associated with clinical

70 Potentiation of Ca(2+) release by cADPR is mediated by increased accumulation of Ca(2+) in

71 ere any significant effects on the rhythm by cADPR overexpression, thus raising questions about the c

72 (cADPR) or photolysis of NPE-cADPR ('caged' cADPR) by ultraviolet laser pulses produced transient ac

73 N1-cIDPR inhibits CD38-catalyzed cADPR hydrolysis with an IC(50) of 0.26 mM.

74 tanding the complex interactions among CD14, cADPR, Ca(2+), and ROS may provide new insights and trea

75 The binary CD38-cADPR model described here represents the most detailed

76 s the first demonstration of a role for CD38-cADPR signaling in a model of inflammatory airway diseas

77 In summary, these data indicate that CD38-cADPR mediates bile acid-induced pancreatitis and acinar

78 In airway smooth muscle, the CD38/cADPR signaling pathway is involved in [Ca2+]i responses

79 Thus, the NO-cGMP-cADPR-Ca2+ pathway, previously described in sea urchin e

80 e first example of a fluorescent N1-cyclized cADPR analogue and is a new pharmacological tool for int

81 of macrophages with the cADPR analog 3-deaza-cADPR or Ca(2+) ionophores recapitulated the effects of

82 ed with the non-metabolizable analog 3-deaza-cADPR, and cytosolic [Ca(2+)] was transiently elevated b

83 cADPR[CH(2)] was 856 nM and that for 3-deaza-cADPR[CH(2)] was 300 nM, about 15- and 5-fold less poten

84 osphonate cyclic 3-deaza-ADP-ribose (3-deaza-cADPR[CH(2)]) showed full agonist activity for release o

85 O-methyl-2'-deoxy-cADPR 9, 8-phenyl-2'-deoxy-cADPR 10 and its ribose counterpart 8-phenyl-cADPR 5 are

86 concentrations, among which 8-bromo-2'-deoxy-cADPR 7 was, unexpectedly, a weak but almost full agonis

87 -cADPR analogues, including 8-bromo-2'-deoxy-cADPR 7, 8-amino-2'-deoxy-cADPR 8, 8- O-methyl-2'-deoxy-

88 g 8-bromo-2'-deoxy-cADPR 7, 8-amino-2'-deoxy-cADPR 8, 8- O-methyl-2'-deoxy-cADPR 9, 8-phenyl-2'-deoxy

89 amino-2'-deoxy-cADPR 8, 8- O-methyl-2'-deoxy-cADPR 9, 8-phenyl-2'-deoxy-cADPR 10 and its ribose count

90 ic syntheses of novel 8-substituted 2'-deoxy-cADPR analogues, including 8-bromo-2'-deoxy-cADPR 7, 8-a

91 ctivate PR-1 expression via an NO-dependent, cADPR-independent pathway.

92 bolites cyclic adenosine 5'-diphosphoribose (cADPR) and ADPR were also present in the superfusates co

93 e identify cyclic adenosine diphosphoribose (cADPR) as an agonist of TRPM2 with dual activity: at con

94 ication of cyclic adenosine diphosphoribose (cADPR) or photolysis of NPE-cADPR ('caged' cADPR) by ult

95 of NAD+ to cyclic adenosine diphosphoribose (cADPR), a Ca2+-mobilizing second messenger, adenosine di

96 Cyclic adenosine diphosphoribose (cADPR), a metabolite of NAD, appears to modulate changes

97 es reveals a loss of specific binding during cADPR, but not IP(3), desensitization.

98 rovide insights into the design of effective cADPR analogs.

99 of effect of postsynaptic infusion of either cADPR antagonist indicates a probable presynaptic site o

100 e of high cytosolic concentrations of either cADPR or its antagonist, 8-amino-cADPR, was ineffective

101 antly more sensitive to NAADP than to either cADPR or InsP3, whereas higher concentrations of NAADP s

102 Oocytes did not respond to either cADPR or NAADP+, but NADP+ and analogues were found to b

103 nsistent with the hypothesis that endogenous cADPR plays an important role during normal contraction

104 38, Thr-221 to Phe, correspondingly enhanced cADPR production, and the double mutation, Thr-221 to Ph

105 The EC(50) for cADPR[CH(2)] was 856 nM and that for 3-deaza-cADPR[CH(2)

106 nt of the RyR complex and a key cofactor for cADPR activity, during RyR/cADPR desensitization.

107 gnaling and provide a functional context for cADPR as a second messenger for Ca2+ influx.

108 The ratio of methanolysis to hydrolysis for cADPR and NAD+ catalyzed by CD38 increases linearly with

109 confirming our previously proposed model for cADPR catalysis.

110 t the activity of the enzyme responsible for cADPR synthesis, ADP-ribosyl (ADPR) cyclase, is rapidly

111 monstrate a potential physiological role for cADPR in modulating cellular Ca(2+) signals via changes

112 ting either that there is a unique route for cADPR synthesis or that a homolog of ADPR cyclase with l

113 (NAD) to cyclic ADP-ribose (cADPR) and from cADPR to ADP-ribose (ADPR).

114 Thus, ADPRC can only generate cADPR from NAD (cyclase), whereas CD38, in contrast, has

115 In addition to NAD, CD38 also hydrolyzed cADPR effectively, and this activity was correspondingly

116 capable of both synthesizing and hydrolyzing cADPR.

117 .5-fold less active than CD38 in hydrolyzing cADPR to ADPR.

118 n contrast, has multiple activities, i.e. in cADPR production and degradation, as well as NAD hydroly

119 the abi1-1 mutation and that an increase in cADPR plays an important role in downstream molecular an

120 hat is activated by nitric oxide to increase cADPR and mobilize Ca(2.)

121 hat biochemical production of cGMP increases cADPR concentration in hippocampal slices in vitro, and

122 e complexities of Ca(2+) signaling involving cADPR, for example, localized release events and propaga

123 intracellular glucose on the ability of IP3, cADPR and CCK to induce cytosolic Ca2+ spikes in pancrea

124 t blockade of cGMP-dependent protein kinase, cADPR receptors, or ryanodine-sensitive Ca2+ stores each

125 e for the development of tools to manipulate cADPR metabolism in vivo.

126 IDPR and 8-NH2-L-cIDPR inhibit CD38-mediated cADPR hydrolysis (IC50 7 muM and 21 microM respectively)

127 generates the calcium-mobilizing metabolite cADPR, make reduced T cell-dependent antibody responses.

128 ctivity: at concentrations above 100 microM, cADPR can gate the channel by itself, whereas lower conc

129 is thus identified as the first C-6 modified cADPR (cyclic adenosine 5'-diphosphoribose) analogue ant

130 blocked the Ca2+-releasing effects of NAADP, cADPR, and caffeine, but not IP3.

131 Exogenous beta-NAD, cADPR, and ADPR (all 100 nm) reduced the release of NE i

132 utive and nerve-evoked overflow of beta-NAD, cADPR, and ADPR in vascular and non-vascular smooth musc

133 Ca2+ spiking [6], the cADPR antagonist 8-NH2-cADPR [7], which blocks cADPR-evoked but not IP3-evoked

134 ular glucose, but the cADPR antagonist 8-NH2-cADPR blocked CCK-evoked Ca2+ spiking only in the absenc

135 te (AMP) specifically inhibits ADPR, but not cADPR-mediated gating of TRPM2, whereas the cADPR antago

136 diphosphoribose (cADPR) or photolysis of NPE-cADPR ('caged' cADPR) by ultraviolet laser pulses produc

137 effect on the Ca (2+)-mobilizing ability of cADPR itself, is an important motif for the antagonistic

138 t study, we directly examined the ability of cADPR to trigger SR Ca2+ release and to modulate Ca(2+)-

139 ession and the consequential accumulation of cADPR play a causal role in mediating cellular different

140 with CD38 expression was the accumulation of cADPR, and both time courses preceded the onset of diffe

141 Despite evidence for the action of cADPR in Arabidopsis, no predicted proteins with signifi

142 research, the precise mechanism of action of cADPR remains uncertain, and experimental findings are c

143 they did not arise through direct actions of cADPR or Ca(2+) on the IP(3)R, but likely resulted from

144 (NAD glycohydrolase), but a trace amount of cADPR is also produced through cyclization of the substr

145 is unable to produce significant amounts of cADPR (<0.02% of reaction products) using NAD(+) as the

146 assay experiments showed that the amounts of cADPR in Arabidopsis thaliana plants increased in respon

147 is study, a novel non-hydrolyzable analog of cADPR, N1-cIDPR (N1-cyclic inosine diphosphate ribose),

148 ibosyl ribose (8-Br-cADPR), an antagonist of cADPR.

149 The effects of antagonists of cADPR signaling, manipulation of cADPR synthesis, and ma

150 The results indicate that the binding of cADPR or cGDPR to the active site induces structural rea

151 controlling the endogenous concentrations of cADPR and NAADP.

152 The production and degradation of cADPR are catalyzed by a family of related enzymes, incl

153 The degradation of cADPR to ADP-ribose was catalyzed by cADPR hydrolase, wh

154 t catalyzes the synthesis and degradation of cADPR.

155 mutation and ABI1 likely acts downstream of cADPR in the ABA-signaling pathway.

156 to antagonize the Ca2+-releasing effects of cADPR on sea urchin egg microsomes and in mammalian cell

157 dulator activity of the metabolic enzymes of cADPR is illustrated.

158 , suggesting that it is the N6-imino form of cADPR that is hydrolyzed by CD38.

159 n at 37 degrees C and measuring formation of cADPR by bioassay and by HPLC.

160 dition of exogenous ABA induced formation of cADPR in T. gondii, stimulated calcium-dependent protein

161 ne of nucleotide cyclization in formation of cADPR to a base-exchange reaction in the generation of N

162 cription of the CD38-catalyzed hydrolysis of cADPR at atomic resolution.

163 bose (cADPR) from NAD+ and the hydrolysis of cADPR to ADP-ribose.

164 processes in the synthesis and hydrolysis of cADPR.

165 l determinants involved in the hydrolysis of cADPR.

166 e with a butyl chain generates inhibitors of cADPR hydrolysis by the human ADP-ribosyl cyclase CD38 c

167 the "northern" ribose in the interaction of cADPR with CD38.

168 athematical simulation of the interaction of cADPR with the circadian clock indicate that cADPR forms

169 The endogenous levels of cADPR in mammalian tissues are primarily controlled by C

170 agonists of cADPR signaling, manipulation of cADPR synthesis, and mathematical simulation of the inte

171 To elucidate the mechanism of cADPR action, we performed confocal Ca(2+) imaging in sa

172 n, provide new insight into the mechanism of cADPR hydrolysis by CD38, and may aid future inhibitor d

173 ssays were used to measure the metabolism of cADPR in sea urchin egg homogenates including a radioimm

174 only in catalysis but also in positioning of cADPR at the catalytic site through strong hydrogen bond

175 e extracts from E2-treated rats, the rate of cADPR inactivation by cADPR hydrolase and the activity o

176 ontrast, we found that there is no rhythm of cADPR levels nor are there any significant effects on th

177 the natural "northern" N1-linked D-ribose of cADPR was replaced by L-ribose.

178 We now report on the role of cADPR in HPV in isolated rat pulmonary arteries and in t

179 Although the role of cADPR in modulating calcium mobilization has been extens

180 egulation of CD38 expression and the role of cADPR-mediated Ca2+ release in airway inflammation.

181 were not, suggesting agonist specificity of cADPR signaling.

182 r results suggest that the primary target of cADPR is the SR Ca(2+) uptake mechanism.

183 s by mechanisms dependent on RyR, but not on cADPR signaling.

184 ; the ryanodine receptors by either NAADP or cADPR, and the IP3 receptors by IP3.

185 nhibit the Ca2+ release elicited by NAADP or cADPR.

186 ependent of inositol 1,4, 5-trisphosphate or cADPR since antagonists of either of these two messenger

187 Both 2'-P-cADPR and cADPR appear to act by a similar mechanism bas

188 that are associated with clinical pathology, cADPR and CD38 represent novel drug targets with potenti

189 xamined the effects of the membrane-permeant cADPR antagonist, 8-bromo-cADPR (8Br-cADPR), on the [Ca2

190 ed pulmonary arteries, the membrane-permeant cADPR antagonist, 8-bromo-cADPR, blocked sustained HPV b

191 cADPR 10 and its ribose counterpart 8-phenyl-cADPR 5 are reported, including improved syntheses of es

192 tch pipette/intracellular solution prevented cADPR from evoking Ca2+ spiking.

193 8 to catalyze an enzyme reaction and produce cADPR, ADPR, and/or nicotinamide.

194 identified and both cyclized NAD to produce cADPR.

195 use NAD as a substrate, the cyclase produces cADPR, whereas CD38 produces mainly ADP-ribose (ADPR).

196 Mutating Phe-174 indeed reduced cADPR production but enhanced ADPR production, convertin

197 n ADP-ribosyl cyclase inhibitor that reduces cADPR and NAADP synthesis in mouse membrane fractions, w

198 Cyclic ADP ribose (cADPR) has been shown to trigger Ca2+ release from intra

199 Cyclic ADP ribose (cADPR) is a Ca(2+)-mobilizing intracellular second messe

200 Cyclic ADP ribose (cADPR) is a calcium-mobilizing metabolite that regulates

201 n of the second-messenger cyclic ADP ribose (cADPR), which controls release of intracellular calcium

202 aling molecules, cGMP and cyclic ADP ribose (cADPR), which function downstream of NO in animals, also

203 ncing regulation, and for cyclic ADP ribose (cADPR)-dependent Ca(2+) signaling.

204 ies in part by increasing cyclic ADP-ribose (cADPR) accumulation in the smooth muscle and, thereby, C

205 l trisphosphate (IP3) and cyclic ADP-ribose (cADPR) all mobilized Ca2+ from internal stores but only

206 yR), the second messenger cyclic ADP-ribose (cADPR) also accelerates the activity of SERCA pumps, whi

207 talyzes the production of cyclic ADP-ribose (cADPR) and ADP-ribose (ADPR) from its substrate, NAD(+).

208 ine dinucleotide (NAD) to cyclic ADP-ribose (cADPR) and from cADPR to ADP-ribose (ADPR).

209 Cyclic ADP-ribose (cADPR) and hydrogen peroxide (H2O2) can facilitate ADPR-

210 ilizing second messengers cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate

211 ng two Ca(2+) messengers, cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate

212 of two Ca(2+) messengers, cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate

213 Cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate

214 NAD(+) acts partially via cyclic ADP-ribose (cADPR) and subsequent release of Ca(2+).

215 ide phosphate (NAADP) and cyclic ADP-ribose (cADPR) are Ca(2+)-mobilizing messengers important for mo

216 viously demonstrated that cyclic ADP-ribose (cADPR) elicits Ca2+ release in airway smooth muscle (ASM

217 talyzing the synthesis of cyclic ADP-ribose (cADPR) from NAD+ and the hydrolysis of cADPR to ADP-ribo

218 Cyclic ADP-ribose (cADPR) has recently been proposed as an endogenous activ

219 Analogues of cyclic ADP-ribose (cADPR) incorporating a methylenebisphosphonate linkage i

220 Cyclic ADP-ribose (cADPR) induces intracellular Ca2+ ([Ca2+]i) release in a

221 Cyclic ADP-ribose (cADPR) is a Ca(2+)-mobilizing cyclic nucleotide derived

222 Cyclic ADP-ribose (cADPR) is a calcium mobilization messenger important for

223 Cyclic ADP-ribose (cADPR) is a potentially important intracellular Ca2+ rel

224 Cyclic ADP-ribose (cADPR) is a universal calcium messenger molecule that re

225 eptor (RyR) activation by cyclic ADP-ribose (cADPR) is followed by homologous desensitization.

226 ded for antagonism at the cyclic ADP-ribose (cADPR) receptor are unclear.

227 -ribose, an antagonist of cyclic ADP-ribose (cADPR) signaling at RyR (S2/S1=0.48+/-0.13).

228 Cyclic ADP-ribose (cADPR) was identified as a signaling molecule in the ABA

229 Cyclic ADP-ribose (cADPR) was previously shown to activate transient expres

230 nthesis and hydrolysis of cyclic ADP-ribose (cADPR), a Ca(2+) messenger molecule responsible for regu

231 ponsible for metabolizing cyclic ADP-ribose (cADPR), a Ca(2+) messenger.

232 2-GUS in response to ABA, cyclic ADP-ribose (cADPR), and Ca2+.

233 es that produce peroxide, cyclic ADP-ribose (cADPR), nicotinamide adenine dinucleotide phosphate (NAA

234 Ca2+-releasing messenger, cyclic ADP-ribose (cADPR), which activates ryanodine receptors, has so far

235 cleotide second messenger cyclic ADP-ribose (cADPR), which is generated by an ectoenzyme ADP-ribosyl

236 5-trisphosphate (IP3) and cyclic ADP-ribose (cADPR).

237 ond messengers: IP(3) and cyclic ADP-ribose (cADPR).

238 ving the second messenger cyclic ADP-ribose (cADPR).

239 Methylenebisphosphonate cyclic ADP-ribose (cADPR[CH(2)]) and methylenebisphosphonate cyclic 3-deaza

240 cADP-Ribose (cADPR) is a novel endogenous messenger that is believed

241 Cyclic adenosine 5'-diphosphate ribose (cADPR) analogs based on the cyclic inosine 5'-diphosphat

242 able cyclic adenosine 5'-diphosphate ribose (cADPR) analogues are chemical biology tools that can pro

243 agents: cyclic adenosine diphosphate ribose (cADPR) from nicotinamide adenine dinucleotide (NAD) and

244 ding cyclic adenosine 5'-diphosphate ribose (cADPR), and CD38 knockout studies have revealed the rele

245 bolite, cyclic adenosine diphosphate ribose (cADPR), from nicotinamide adenine dinucleotide (NAD(+)).

246 ount of cyclic adenosine diphosphate ribose (cADPR).

247 olecule cyclic adenosine diphosphate ribose (cADPR).

248 olecule cyclic adenosine diphosphate ribose (cADPR).

249 of the cyclic adenosine diphosphate ribose (cADPR)/ryanodine-sensitive stores but not the inositol t

250 and cyclic adenosine 5'-diphosphate-ribose (cADPR) are established Ca2+-mobilizing messengers that a

251 3)) and cyclic adenosine diphosphate-ribose (cADPR) are second messengers that enhance neurosecretion

252 lin and cyclic adenosine diphosphate-ribose (cADPR).

253 lic adenosine dinucleotide phosphate ribose (cADPR) in regulating the latter have proven equivocal.

254 alcium messenger molecule, cyclic ADP-ribose(cADPR).

255 key cofactor for cADPR activity, during RyR/cADPR desensitization.

256 ein, most likely the RyR itself, mediate RyR/cADPR desensitization and resensitization, respectively.

257 From the substrate side, cADPR is found to change its conformation to fit into th

258 Since cADPR/ryanodine-sensitive stores are implicated in the C

259 he membrane permeant, hydrolytically stable, cADPR receptor agonist 8-Br-N1-cIDPR via regio- and ster

260 rved that all-trans-retinoic acid stimulates cADPR synthesis by ADP ribose cyclase (ADPR cyclase) in

261 )] i ) through PKA activation and subsequent cADPR generation.

262 ture-activity relationships of 8-substituted cADPR analogues in both Jurkat T-lymphocytes and sea urc

263 the antagonistic activities of 8-substituted cADPR analogues.

264 es reveal that both the enzyme and substrate cADPR undergo catalysis-associated conformational change

265 00 nM, about 15- and 5-fold less potent than cADPR, respectively.

266 hibition of the SR Ca(2+) with thapsigargin, cADPR failed to produce any increase in sparking activit

267 ated monocyte-induced RPE apoptosis and that cADPR contributes to these changes.

268 We conclude that cADPR and NAADP, in combination with ADPR, represent phy

269 Here, we provide evidence that cADPR-mediated signaling pathways play a key role in ind

270 In all cases, we found that cADPR modulates intracellular free calcium levels in cel

271 cADPR with the circadian clock indicate that cADPR forms a feedback loop within the plant circadian c

272 We previously reported that cADPR, produced by the ADP-ribosyl cyclase, CD38, contro

273 ited by acetylcholine (ACh), suggesting that cADPR is involved during muscarinic receptor activation.

274 ine monophosphate (AMP), which suggests that cADPR and NAADP lead to mobilization of endogenous ADPR

275 uppressed by 8-Br-cADPR, which suggests that cADPR and NAADP share a common binding site on TRPM2 tha

276 The cADPR antagonist 8-bromo-cADPR attenuated the Ca2+ respo

277 The cADPR hydrolase activity of the two mutants was similarl

278 cADPR evoke repetitive Ca2+ spiking [6], the cADPR antagonist 8-NH2-cADPR [7], which blocks cADPR-evo

279 y of all the mutants was plotted against the cADPR hydrolase activity.

280 ]i) release in airway smooth muscle, and the cADPR antagonist, 8-amino-cADPR, abolishes [Ca2+]i oscil

281 We previously demonstrated that CD38 and the cADPR generated by CD38 regulate calcium signaling in le

282 or absence of intracellular glucose, but the cADPR antagonist 8-NH2-cADPR blocked CCK-evoked Ca2+ spi

283 Similar to the membrane-bound cyclase, the cADPR hydrolase activity was also independent of cGMP.

284 pharmacological tool for intervention in the cADPR pathway of cellular signaling.

285 odine receptors was suggested to mediate the cADPR-dependent pathway, because ruthenium red, an antag

286 ment with either nicotinamide (20 mM) or the cADPR antagonist 8-Br-cADPR (30 muM) abrogated TLCS-indu

287 evoke Ca2+ spiking via either the IP3 or the cADPR pathway.

288 In addition, we show that the cADPR antagonist blocks the chemotaxis of human monocyte

289 We suggest that the cADPR signaling system plays an important role in the re

290 , inhibited the mGluR response only when the cADPR-dependent pathway was isolated by blocking the IP(

291 cADPR-mediated gating of TRPM2, whereas the cADPR antagonist 8-Br-cADPR exhibits the reverse block s

292 effects of NAD(+) on TGF-beta1, whereas the cADPR antagonist 8-Br-cADPR, Ca(2+) chelation, and antag

293 Whether the cADPR signaling pathway is common to agonists acting thr

294 Treatment of macrophages with the cADPR analog 3-deaza-cADPR or Ca(2+) ionophores recapitu

295 Thus, cADPR regulates calcium signaling of a discrete subset o

296 Exposure of the cells to cADPR resulted in a slow (>2 minutes) and steady increas

297 In this study, we examine whether cADPR is required for chemotaxis of human monocytes and

298 We have now investigated whether cADPR may play a signaling role in action of beta-estrad

299 ol for determining the pathway through which cADPR mediates Ca(2+) release.

300 e human CD38 enzymatic domain complexed with cADPR at 1.5-A resolution, with its analog, cyclic GDP-r

301 These effects were not evident with cADPR alone or following cytosolic Ca(2+) elevation alon