ライフサイエンスコーパス: PDE

1 PDE activity is required for robust replication in myelo

2 PDE activity was measured in human atrial tissue from pa

3 PDE is caused by mutations in ALDH7A1, also known as ant

4 PDE levels of PDGF-AA, platelet glycoprotein VI, integri

5 PDEs controlling natriuretic-peptide-coupled cGMP remain

6 including activation of phosphodiesterase-1 (PDE-1), dampen the rise of cGMP.

7 dback loop, mediated by phosphodiesterase-2 (PDE-2) and stimulated by cGMP-dependent kinase (PKG), un

8 Modulation of 2'-PDE represents a unique therapeutic approach for regulat

9 f 2',5'-oligoadenylate phosphodiesterase (2'-PDE), a key regulatory enzyme of the interferon pathway.

10 tuberculosis-infected mice receiving type 4 PDE-Is (rolipram and cilomilast) and the impact on bacte

11 Type 4 PDE-Is may increase the severity of tuberculosis and sho

12 The type 4 PDE-Is rolipram and cilomilast accelerated the time to d

13 to clearance, and relapse when types 3 and 5 PDE-Is (cilostazol and sildenafil, respectively) and rol

14 Thus, VP3-CTD is a 2',5'-PDE able to functionally substitute for ns2 in MHV infec

15 acterially expressed VP3-CTD exhibited 2',5'-PDE activity, which cleaved 2-5A in vitro.

16 ecting both humans and animals, encode 2',5'-PDEs capable of antagonizing RNase L.

17 With this system, we found that 2',5'-PDEs encoded by the human coronavirus HCoV-OC43 (OC43; a

18 iruses encode proteins with homologous 2',5'-PDEs that antagonize activation of innate immunity.

19 showed that 2',5'-phosphodiesterases (2',5'-PDEs) encoded by the prototypical Betacoronavirus, mouse

20 -CoV, encode 2',5'-phosphodiesterases (2',5'-PDEs) that antagonize the OAS-RNase L pathway, and we re

21 The consistent structural alignment of 57 PDE ligand binding site residues enables the systematic

22 ls by deletion of the pdeA gene coding for a PDE promoted biofilm formation in Streptococcus mutans.

23 We show that pGpG inhibits a PDE-A from Pseudomonas aeruginosa.

24 es to show that the isolated EAL domain of a PDE from Escherichia coli (YahA) is in a fast thermodyna

25 This is the first description of a PDE specifically involved in NO-induced biofilm dispersi

26 ase A (PKA) R-subunit through formation of a PDE-PKAR-cyclic adenosine monophosphate (cAMP) complex (

27 idence suggests that CdgA is predominantly a PDE, while CdgB is predominantly a DGC.

28 specifically inhibited DisA but not YybT (a PDE) whilst TA was more promiscuous and inhibited both D

29 9,10-tetrahydrobenzo[a]pyrene (dG-N (2) -B[a]PDE) were not detected in any specimen, whereas N-(deoxy

30 8,9,10-tetrahydrobenzo[a]pyrene (dG-N(2)-B[a]PDE); the aromatic amine 4-aminobiphenyl (4-ABP), N-(deo

31 of cAMP signal amplification by accelerated PDE-mediated cAMP turnover.

32 ium spiny neuron-enriched and cGMP-activated PDE, in AMPAR trafficking.

33 e rate of cGMP hydrolysis by light-activated PDE is diffusion limited, which is not the case for spon

34 effects of these proteins on light-activated PDE* decay may be responsible for the quickening of resp

35 orating an effect of GRK1 on light-activated PDE* decay rate can satisfactorily account for the chang

36 n also modulate the decay of light-activated PDE*, and the effects of these proteins on light-activat

37 me, thereby reducing the number of activated PDE molecules.

38 is not the case for spontaneously activated PDE.

39 nd) form of Tr*, we found that Tr* activated PDE at a similar efficiency in rods and cones.

40 segment of a mouse rod only a few activated PDEs are sufficient to generate a signal that overcomes

41 By activating PDE with known concentrations of the active (guanosine 5

42 red MHYT domain support NbdA being an active PDE.

43 A larger number of spontaneously active PDEs decreases dark noise, thereby improving detection o

44 In addition, PDE-5 inhibitors may prove to be innovative therapeutic

45 Additionally, PDEs encoded by OC43 and BEV rescue MHV(Mut) replication

46 we show that atropine acts as an allosteric PDE type 4 (PDE4) inhibitor.

47 MucR displayed both diguanylate cyclase and PDE activity in vitro, which seemed regulated in a growt

48 larly on those proteins bearing both DGC and PDE modules, and for future optimization studies to targ

49 In a dual DGC and PDE-A reaction, excess pGpG extends the half-life of c-d

50 Elevated EDE and PDE levels of atherosclerosis-promoting proteins in CeVD

51 osphodiesterase-5 (PDE5) gene expression and PDE activity is significantly reduced in penile tissues

52 drug molecules, including COX, ACE, MAO, and PDE inhibitors, have been successfully [(18)F]-labeled i

53 In this study, PKAR and PDE from Dictyostelium discoideum (RD and RegA, respecti

54 , allowing optimization of PDE1B potency and PDE selectivity.

55 ria typically encode many different DGCs and PDEs within their genomes.

56 a sophisticated interaction between DGCs and PDEs.

57 exogenously provided cholesterol augmented, PDE inhibitor-induced steroidogenesis, suggesting that t

58 ion may provide a further level of bacterial PDE regulation.

59 PDE6C increased the basal PDE activity and speeded the rate-limiting step for phot

60 tigated pharmacokinetic interactions between PDE-Is (cilostazol and sildenafil) and rifampin.

61 ssociation from sGC, and cGMP degradation by PDE, exerted a dominant influence on cGMP accumulation r

62 The termination phase is initiated by PDEs actively targeting the protein kinase A (PKA) R-sub

63 P-mediated sequestration of the R-subunit by PDEs.

64 study, we identify PDE10A as the major cAMP PDE in mouse striatum and monitor PKA-dependent PDE10A p

65 ting for only a small fraction of renal cAMP PDE activity.

66 PKA/EPAC that are regulated by specific cAMP-PDEs (the PDE-regulated phosphoproteomes).

67 substructure analysis of the cocrystallized PDE ligands in combination with those in the ChEMBL data

68 its, this mechanism is able to use a cyclase/PDE enzyme pair to dynamically control a cyclic nucleoti

69 Herein, we demonstrate PDE-4 inhibition as a therapeutic strategy to ameliorate

70 show that calcium- and calmodulin-dependent PDEs (PDE1A and PDE1C) and PDE3A modulate the developmen

71 and inhibited the activity of EAL-dependent PDEs (PA2133, PvrR, and purified recombinant RocR) from

72 pG exert product inhibition on EAL-dependent PDEs, thereby increasing intracellular c-di-GMP in Delta

73 novicida strains lacking either the two DGC/PDE genes (cdgA and cdgB) or the entire gene cluster (st

74 reus produces a second cytoplasmic DHH/DHHA1 PDE Pde2.

75 The role of different PDE isozymes, particularly PDE3A vs PDE3B, in the regula

76 n be defined by their responses to different PDE inhibitors.

77 ogy for understanding the roles of different PDEs in the regulation of cyclic nucleotide signaling.

78 ynergistic relationships among the different PDEs that coordinate cAMP-signaling cascades in these ce

79 ylation occurs unless at least two different PDEs are concurrently inhibited in these cells.

80 In Jurkat cells we find multiple, distinct PDE-regulated phosphoproteomes that can be defined by th

81 osphoproteome analyses of myocytes with each PDE selectively inhibited reveals substantial differenti

82 lated from the peritoneal dialysis effluent (PDE) of noninfected uremic patients.

83 ter benefits compared with inhibiting either PDE alone.

84 nditions, stationary powder disk electrodes (PDEs) made from Fe/FeO and Fe/FeS were characterized usi

85 levels via overexpression of genes encoding PDEs.

86 previously published pseudopodium-enriched (PDE) protein/phosphoprotein datasets to identify novel P

87 ividuals with pyridoxine-dependent epilepsy (PDE).

88 solution of a partial differential equation (PDE).

89 Partial differential equations (PDE) were built to model a radially symmetric reaction-d

90 ric MHV system (MHV(Mut)) in which exogenous PDEs were expressed from an MHV backbone lacking the gen

91 osomes (EDEs) and platelet-derived exosomes (PDEs) were precipitated and enriched separately by immun

92 e enzyme PDE10A is the most highly expressed PDE in striatal medium-sized spiny neurons (MSNs) with l

93 They also suggest that in order for PDE inhibitor therapy to be an effective stimulator of s

94 An important role for PDE was supported by the lack of inhibition of the lipol

95 Overproduction of the GdpP PDE greatly sensitized cells to beta-lactam antibiotics.

96 ution in the HD dyad caused loss of c-di-GMP PDE activity and of two iron atoms.

97 xylate active site can catalyze the c-di-GMP PDE reaction and that this activity can be redox regulat

98 d biochemical characterization of a c-di-GMP PDE, PdcA, 1 of 37 confirmed or putative c-di-GMP metabo

99 One class of c-di-GMP PDEs contains a characteristic HD-GYP domain.

100 Here we report that an HD-GYP PDE from Vibrio cholerae contains a non-heme diiron-carb

101 These constraints explain the higher PDE density in mammalian compared with amphibian rods th

102 ture shows the characteristic folds of human PDE enzymes but also contains the parasite-specific P-po

103 he screen of the inhibitory potency of human PDE inhibitors against TcrPDEC, implies that the scaffol

104 DEC, implies that the scaffold of some human PDE inhibitors might be used as the starting model for d

105 Being responsible for cAMP hydrolysis, PDEs are likely to play a role in this setting.

106 d on an analysis of the phosphodiesterase I (PDE I)-mediated size variation of a fluorescein-labeled

107 In PDE cortex, antiquitin immunofluorescence was greatly at

108 gative modulator of TLRs that we detected in PDE, inhibited PDE-induced, TLR2- or TLR4-mediated profi

109 ught to determine age-related differences in PDE activity and associated intracellular signaling resp

110 tribution of antiquitin, its distribution in PDE, and associated brain malformations.

111 l cells in the brain, and its dysfunction in PDE is associated with neuronal migration abnormalities

112 the large diversity of chemical scaffolds in PDE ligands.

113 bsence (with GTPgammaS) of Tr* inactivation, PDE activation required more light (and was therefore le

114 ant of MHV (ns2(H126R)) encoding an inactive PDE fails to antagonize RNase L activation and replicate

115 ne is limited by counter-adaptions including PDE upregulation.

116 nduced dispersion was supported by increased PDE activity, resulting in decreased c-di-GMP levels in

117 Moreover, increased PDE activity was mainly due to a transcriptional activat

118 tion of pGpG in the orn strain could inhibit PDE-As, increasing c-di-GMP concentration.

119 r of TLRs that we detected in PDE, inhibited PDE-induced, TLR2- or TLR4-mediated profibrotic response

120 Phosphodiesterase inhibitors (PDE-Is) have been shown to be beneficial in animal model

121 cAMP levels, PDE activity, and phospholamban phosphorylation (pPLB) w

122 games for which the behavior of the limiting PDE is not known.

123 data suggest that whereas PDE4 is the major PDE isoform involved in the regulation of global intrace

124 luding delivery via the inhaled route, mixed PDE inhibitors and/or antisense biologicals targeted tow

125 Our results using PDE8 as a model PDE, reveal that PDEs mediate active hydrolysis of cAMP

126 Whereas most PDEs have accessory domains that are involved in the reg

127 en together, these data reveal that multiple PDEs work in concert to regulate three of the important

128 polysis in brown adipocytes, whereas neither PDE inhibitor alone had any substantial effect under bas

129 mising drug target with the emergence of new PDE inhibitors and a novel PKA target protein, HSP20, wh

130 o imaging data were also fit well by the new PDE model, with estimates of the dissociation constant (

131 ce of well-established and potentially novel PDE-dependent mechanisms that regulate cGMP under physio

132 cellular levels of cAMP by cyclic nucleotide PDE inhibition both suppresses the immune response and i

133 ary and partial differential equations (ODEs/PDEs).

134 we examined the efficiency of activation of PDE by activated Tr (Tr*).

135 Processing of BdlA leads to activation of PDE DipA, which results in a net reduction of c-di-GMP a

136 Histologic analysis of PDE cortex revealed areas of abnormal radial neuronal or

137 residues enables the systematic analysis of PDE-ligand interaction fingerprints (IFPs), the identifi

138 E8-RIalpha complex represents a new class of PDE-based complexes for specific drug discovery targetin

139 In a comparison of PDE activation in the presence (with GTP) and absence (w

140 y regulating the splicing and degradation of PDE transcripts.

141 ed to an ongoing surge in the development of PDE inhibitors as lead compounds for trypanocidal drugs.

142 remaining difference in the effectiveness of PDE activation between rods and cones.

143 The lower effectiveness of PDE activation in carp cones is due partly to the fact t

144 Furthermore, we examine the effects of PDE-4 inhibition by pharmacologic treatment in the fragi

145 We assessed the impact of PDE-Is on the duration of treatment in tuberculous mice.

146 We demonstrate that acute inhibition of PDE-4 by pharmacologic treatment in hippocampal slices r

147 pharmacological and genetic manipulation of PDE activity, we found that the rise in cAMP resulting f

148 brain tissue was utilized for measurement of PDE-associated metabolites and Western blot analysis.

149 mutant TNNT2 and epigenetic modifications of PDE genes in both DCM iPSC-CMs and patient tissue.

150 vel, it is not clear whether perturbation of PDE alone, under oxidative stress, is the best approach

151 he GAF ligand with the catalytic reaction of PDE.

152 gest that a disturbance in the regulation of PDE-coupled CNs linked to N-type Ca(2+) channels is an e

153 erstanding of the structural requirements of PDE binding that will be useful in future drug discovery

154 p54(nrb)/NONO in regulating the stability of PDE transcripts by facilitating the interaction between

155 In vitro studies of PDE IVb inhibition by enantiomeric pyrrolizidinones (+)-

156 )/NONO regulates the splicing of a subset of PDE isoforms.

157 to understand the regulation and function of PDEs in SMC pathogenesis of vascular diseases.

158 This review discusses the involvement of PDEs in airway diseases and various strategies that are

159 is the first instance, to our knowledge, of PDEs directly interacting with a cAMP-receptor protein i

160 en the I-site of DGCs and the active site of PDEs; this molecule represents a novel tool for mechanis

161 tely integrable hydrodynamic-type systems of PDEs - which provides explicit finite-size solutions, ma

162 icellular systems require solving systems of PDEs for release, uptake, decay and diffusion of multipl

163 the Protein Data Bank (PDB) with a focus on PDE-ligand interactions.

164 ains to be identified, and PDE10 is the only PDE activated by cAMP.

165 PDE1 is the only PDE family activated by Ca(2+), which is reduced in PKD

166 aling is characterized by individual DGCs or PDEs that are specifically associated with downstream c-

167 ficity signaling is characterized by DGCs or PDEs that modulate a general signal pool, which, in turn

168 0.49, and >5000-fold selectivity over other PDEs, fully attenuates MK-801-induced hyperlocomotor act

169 n but enhanced selectivity against the other PDEs.

170 as the starting model for design of parasite PDE inhibitors.

171 In addition, PdcA PDE activity is allosterically regulated by GTP, further

172 d ADORA2B signaling underlies reduced penile PDE activity by decreasing PDE5 gene expression in a HIF

173 Phosphodiesterase (PDE) 10A is an enzyme involved in the regulation of cycl

174 Phosphodiesterase (PDE) 8A and PDE8B are high-affinity, cAMP-specific phosp

175 s is presented of the 220 phosphodiesterase (PDE) catalytic domain crystal structures present in the

176 rotein 2 (ns2) is a 2',5'-phosphodiesterase (PDE) that cleaves 2-5A, thereby antagonizing RNase L act

177 and that treatment with a phosphodiesterase (PDE) 4 inhibitor rolipram rescues the decrease in cAMP.

178 portion of p70 includes a phosphodiesterase (PDE) domain and an oligonucleotide/oligosaccharide bindi

179 superfamily member, is a phosphodiesterase (PDE) that cleaves 2-5A, thereby preventing activation of

180 ombination therapy with a phosphodiesterase (PDE)-4 inhibitor.

181 h encodes a cyclic-di-AMP phosphodiesterase (PDE).

182 anylate cyclase (DGC) and phosphodiesterase (PDE) enzymes that produce and degrade c-di-GMP, respecti

183 cyclase (DGC) enzymes and phosphodiesterase (PDE) enzymes, which synthesize and degrade c-di-GMP, res

184 hat produces c-di-AMP and phosphodiesterase (PDE) that degrades c-di-AMP.

185 lymphocytes (CRTh2), and phosphodiesterase (PDE)-4 inhibitors.

186 dulation by drugs such as phosphodiesterase (PDE)-5 inhibitors and guanylate cyclase activators may r

187 enzymes and hydrolyzed by phosphodiesterase (PDE) enzymes.

188 use of its degradation by phosphodiesterase (PDE)4 and cannot access the intracellular sarcoplasmic r

189 sine monophosphate (cAMP) phosphodiesterase (PDE), PDE4, is expressed in human atrium and contributes

190 s to activate 50% of cGMP phosphodiesterase (PDE).

191 /DHHA1) domain-containing phosphodiesterase (PDE) GdpP, S. aureus produces a second cytoplasmic DHH/D

192 ors of the cGMP-degrading phosphodiesterase (PDE) 5 have achieved blockbuster status in the treatment

193 ion of c-di-GMP-degrading phosphodiesterase (PDE) activity.

194 re, we show that the dual phosphodiesterase (PDE)7- glycogen synthase kinase (GSK)3 inhibitor, VP3.15

195 of clinically established phosphodiesterase (PDE) families.

196 and a C-terminal c-di-GMP phosphodiesterase (PDE) domain.

197 our effort in identifying phosphodiesterase (PDE) 4B-preferring inhibitors for the treatment of centr

198 differential switching in phosphodiesterase (PDE) activity.

199 he expression of multiple phosphodiesterase (PDE) isoforms, including PDE2A, PDE3A, PDE3B, PDE4A, PDE

200 l 3',5'-cyclic nucleotide phosphodiesterase (PDE) inhibitors, concentrating on both experimental and

201 tors of cyclic nucleotide phosphodiesterase (PDE) PDE3A have inotropic actions in human myocardium, b

202 t combining inhibitors of phosphodiesterase (PDE) 3 and PDE4 provides greater benefits compared with

203 se A to the activation of phosphodiesterase (PDE) 3A, PDE4A, and PDE4B but not of PDE4D.

204 latation is inhibition of phosphodiesterase (PDE)3, but the antiinflammatory effect may be due to inh

205 On average around one phosphodiesterase (PDE) molecule is spontaneously active per mouse compartm

206 ens identified 8 as a pan-phosphodiesterase (PDE) family inhibitor, which was implicated in a sustain

207 kinase A (PKA)-regulated phosphodiesterase (PDE) 4D3 binds to A kinase-anchoring proteins (AKAPs).

208 32%), and 500 muM of the phosphodiesterase (PDE) inhibitor isobutylmethylxanthine (by 33%).

209 memory formation, but the phosphodiesterase (PDE) involved remains unknown.

210 RET approach and in vitro phosphodiesterase (PDE) activity assays, we show that atropine acts as an a

211 Phosphodiesterases (PDE-As) end signaling by linearizing c-di-GMP to 5'-phos

212 n of cAMP degradation by phosphodiesterases (PDE) likely has an important role, because cAMP is inact

213 cellular cAMP gradients, phosphodiesterases (PDE) mediate fundamental aspects of brain function relev

214 Phosphodiesterases (PDEs) are a family of enzymes that break down cGMP and c

215 Phosphodiesterases (PDEs) are a superfamily of enzymes that catalyze the bre

216 Phosphodiesterases (PDEs) are enzymes responsible for catalyzing hydrolysis

217 late cyclases (DGCs) and phosphodiesterases (PDEs) control c-di-GMP homeostasis in the cell.

218 ynthesizing c-di-GMP and phosphodiesterases (PDEs) for degrading c-di-GMP.

219 nylyl cyclases (ACs) and phosphodiesterases (PDEs) since their discoveries 40 years ago, downstream c

220 ) and cAMP hydrolysis by phosphodiesterases (PDEs) (termination phase).

221 levels are regulated by phosphodiesterases (PDEs), with PDE4s predominantly responsible for cAMP deg

222 lases and degradation by phosphodiesterases (PDEs).

223 yclic nucleotide coupled phosphodiesterases (PDEs) play a key role limiting the hydrolysis of cAMP an

224 tors, adenylyl cyclases, phosphodiesterases (PDEs)), and receptor tyrosine kinases involved in growth

225 GMP (c-di-GMP)-degrading phosphodiesterases (PDEs) and the chemosensory protein BdlA, with BdlA playi

226 atalytic site of the EAL phosphodiesterases (PDEs).

227 e cAMP-degrading enzymes phosphodiesterases (PDEs) play a key role in shaping local changes in cAMP.

228 cAMP-degrading enzymes, phosphodiesterases (PDEs), localise to specific subcellular domains within w

229 le, c-di-GMP hydrolysing phosphodiesterases (PDEs) have been identified as key targets to aid develop

230 then directly modulates phosphodiesterases (PDEs), ion-gated channels, or cGMP-dependent protein kin

231 lass I cyclic nucleotide phosphodiesterases (PDEs) are critical for regulation of cyclic nucleotide s

232 Cyclic nucleotide phosphodiesterases (PDEs) catalyze the breakdown of cAMP, thereby regulating

233 ferent cyclic nucleotide phosphodiesterases (PDEs) have not yet been identified in most cell types.

234 sis by cyclic nucleotide phosphodiesterases (PDEs) is a critical determinant of the amplitude, durati

235 making cyclic nucleotide phosphodiesterases (PDEs) potential regulators of synaptic strength.

236 ety of cyclic nucleotide phosphodiesterases (PDEs), which play a critical role in the regulation of c

237 ted by cyclic nucleotide phosphodiesterases (PDEs).

238 effects of inhibition of phosphodiesterases (PDEs).

239 ylate cyclases (DGCs) or phosphodiesterases (PDEs) were screened for their involvement in low-tempera

240 al c-di-GMP synthases or phosphodiesterases (PDEs).

241 ctivity versus the other phosphodiesterases (PDEs).

242 ded by c-di-GMP-specific phosphodiesterases (PDEs).

243 yclases and cdG-specific phosphodiesterases (PDEs).

244 the latter via specific phosphodiesterases (PDEs).

245 iPSC-CMs, we found that phosphodiesterases (PDEs) 2A and PDE3A were upregulated in DCM iPSC-CMs and

246 been recently shown that phosphodiesterases (PDEs) can catalyze dissociation of bound cAMP and thereb

247 be hydrolyzed by various phosphodiesterases (PDEs).

248 regulate the dynamic interplay between PKAR, PDE, and cAMP are unclear.

249 ysine metabolites were present in postmortem PDE cortex.

250 syntheses of GlaxoSmithKline's highly potent PDE IVb inhibitor 1 were developed.

251 we identified that Orn serves as the primary PDE-B enzyme that removes pGpG, which is necessary to co

252 y activity, as well as SureChEMBL for recent PDE related patents, to provide a wider context for expl

253 of PDE1, the only family of Ca(2+)-regulated PDEs, also induced a mitogenic response to AVP in NHK ce

254 th BdlA playing a pivotal role in regulating PDE activity and enabling dispersion in response to a wi

255 selectivity (>6000-fold) over other related PDEs but with a poor pharmacokinetic profile.

256 ole of cAMP hydrolysis and the most relevant PDEs in the pathogenesis of PKD, we examined cyst develo

257 The RVA PDE forms the carboxy-terminal domain of the minor core

258 vated form of sGC, and phosphodiesterase(s) (PDE).

259 between the exoribonuclease XRN2 and select PDE transcripts.

260 )/NONO led to increased expression of select PDE isoforms revealed that p54(nrb)/NONO regulates the s

261 he effect of specific inhibition of selected PDEs on cardiac myocyte hypertrophic growth.

262 ew insights into how conserved and selective PDE interaction hot spots can accommodate the large dive

263 tabases ChEMBL and PDB for fragments showing PDE inhibitory activity, as well as SureChEMBL for recen

264 tis in children worldwide, encodes a similar PDE.

265 demonstrate that inactivation of this single PDE gene is sufficient to impact multiple c-di-GMP-depen

266 FPs), the identification of subtype-specific PDE-ligand interaction features, and the classification

267 Conventional approaches to study PDE function typically rely on measurements of global cA

268 odiesterase 10A (PDE10A) is a dual substrate PDE that can hydrolyze both cGMP and cAMP.

269 molecules by yet unidentified enzymes termed PDE-Bs.

270 ontent, and significantly higher levels than PDEs of the endothelial proteins vascular cell adhesion

271 sults using PDE8 as a model PDE, reveal that PDEs mediate active hydrolysis of cAMP bound to its rece

272 It was recently shown that PDEs interact with PKAR to initiate the termination phas

273 The PDE activity of ns2 is required for MHV replication in m

274 Among the PDE superfamily, PDE2 has the unique property of being a

275 Thus, we sought to identify the PDE-B enzyme(s) responsible for pGpG degradation.

276 ytes to endogenous components present in the PDE of noninfected patients.

277 gests a role for substrate channeling in the PDE-dependent dissociation and hydrolysis of cAMP bound

278 ypothesized that daily administration of the PDE-5 inhibitor, tadalafil (TAD) will attenuate inflamma

279 hat are regulated by specific cAMP-PDEs (the PDE-regulated phosphoproteomes).

280 l domain and the linker connecting it to the PDE domain are disordered in the reported crystal struct

281 of cyclic nucleotide degrading enzymes, the PDEs.

282 Therefore, PDE isoform expression and activity strongly influence g

283 These PDEs were selected because of their importance in cross-

284 /-)/B(-/-) mice to determine roles for these PDEs in the regulation of testosterone production.

285 Nearly 80% of these PDEs are predicted to depend on the catalytic function o

286 creasing the expression or activity of these PDEs may, therefore, retard the development of PKD.

287 ants tested, deletions of six DGCs and three PDEs were found to affect these phenotypes at low temper

288 clude nausea, vomiting, and headaches due to PDE inhibition and at higher concentrations to cardiac a

289 Total PDE activity decreased with age, and the relative PDE4 a

290 In addition, total PDE- and PDE3-specific activities were not altered in pe

291 In contrast, higher total PDE and PDE3 activities in adult IDC patients treated wi

292 patients on PDE3i demonstrated higher total PDE-specific (74.6+/-13.8 pmol/mg per minute) and PDE3-s

293 and accounts for approximately 15% of total PDE activity.

294 ing differential roles for each of these two PDEs.

295 -based approach coupled with treatment using PDE isozyme-selective inhibitors to characterize the pho

296 vance, in that this identifies and validates PDE-4 inhibition as potential therapeutic intervention f

297 d endothelial nitric oxide synthase, whereas PDEs had significantly higher levels of platelet glycopr

298 study, we analyzed tissue from a child with PDE as well as control human and murine brain to determi

299 Therapies for some of these disorders with PDE inhibitors have been successful at increasing cGMP l

300 Modeling of these systems with PDE models with Bayesian priors is necessary for quantit