ライフサイエンスコーパス: PDE3

1 ulated by inhibition of phosphodiesterase 3 (PDE3).

2 and PDE4, but not IL-4-induced activation of PDE3.

3 inone and cilostazol, specific inhibitors of PDE3.

4 secretion, its action may be independent of PDE3.

5 efficient membrane association/targeting of PDE3.

6 Combined PDE3/4 inhibition did not induce T cell apoptosis, sugge

7 ognised that the use of PDE3, PDE4 and mixed PDE3/4 inhibitors can provide clinical benefit to patien

8 ced in Pkd2(-/WS25);Pde3a(-/-) mice, despite PDE3 accounting for only a small fraction of renal cAMP

9 on; another cAMP pool that is metabolized by PDE3 activates another PKA (isozyme or pool) which suppr

10 s can be designed with flexible size against PDE3 active site.

11 In contrast, higher total PDE and PDE3 activities in adult IDC patients treated with PDE3i

12 4D, a cGMP-specific PDE, and of particulate PDE3, activities in betaTC3 insulinoma cells.

13 Furthermore, determination of PDE3 activity and PDE3A and PDE3B mRNA levels in heart a

14 lic and microsomal membrane protein for cAMP PDE3 activity assays.

15 istent with our hypothesis that an increased PDE3 activity in aortic smooth muscle cells may contribu

16 Moreover, PDE3 activity is required for insulin/insulin-like growt

17 We find that PDE3 activity is the major low Km cAMP activity in the a

18 Little is known about relative changes in PDE3 activity or gene expression during the evolution of

19 chromatography of solubilized SR membranes, PDE3 activity was recovered in distinct high molecular w

20 Consistent with these observations, PDE3 activity was reduced approximately 8-fold in SR fra

21 regulated, resulting in significantly higher PDE3 activity.

22 tion (P<.05) in microsomal but not cytosolic PDE3 activity.

23 tion of PKA via cGMP-dependent inhibition of PDE3 activity.

24 we found that it required a combination of a PDE3 and a PDE4 inhibitor to fully induce UCP1 mRNA and

25 olysis in microsomal fractions by inhibiting PDE3 and in cytosolic fractions by inhibiting both PDE3

26 p with a methoxy group raised the IC(50) for PDE3 and PDE1, yet only slightly changed the IC(50) for

27 nd in cytosolic fractions by inhibiting both PDE3 and PDE1.

28 or PDE4, but actually lowered the IC(50) for PDE3 and PDE1.

29 e analyzed the in vivo levels of low Km cAMP PDE3 and PDE4 activities as well as PDE3A and PDE3B mRNA

30 lase activities, and stimulate cAMP-specific PDE3 and PDE4 and cGMP-specific PDE5 activities.

31 in (PI3-K inhibitor) inhibited activation of PDE3 and PDE4 by IL-4.

32 We report here that PDE3 and PDE4 expression levels are lower in human ADPKD

33 However, the role of PDE3 and PDE4 in the regulation of cardiomyocyte apoptos

34 he rise in cAMP resulting from inhibition of PDE3 and PDE4 induces hypertrophy, whereas increasing cA

35 This effect was magnified by dual PDE3 and PDE4 inhibition.

36 hese data provide a rationale for the use of PDE3 and PDE4 inhibitors in the treatment of COPD and as

37 tors alone had no effect, the combination of PDE3 and PDE4 inhibitors induced ATF-1/CREB serine 63/13

38 when injected into mice, the combination of PDE3 and PDE4 inhibitors stimulated glucose uptake in BA

39 he coincident signaling of the major cardiac PDE3 and PDE4 isoforms, thus orchestrating a feedback lo

40 firmed by in situ hybridization studies with PDE3 and PDE4 probes.

41 ts suggested that IL-4-induced activation of PDE3 and PDE4 was downstream of IRS-2/PI3-K, not STAT6,

42 Mammalian phosphodiesterases types 3 and 4 (PDE3 and PDE4) hydrolyze cAMP and are essential for the

43 Mammalian phosphodiesterase types 3 and 4 (PDE3 and PDE4) hydrolyze cAMP and are essential for the

44 erent TCC contained different proportions of PDE3 and PDE4, and their activities increased during Ag

45 drolyzing phosphodiesterases (PDEs), such as PDE3 and PDE4, coexist in cardiomyocytes and elicit diff

46 ant MBP epitope (amino acids 83-99), contain PDE3 and PDE4, two PDEs that exhibit a high affinity for

47 tivated cyclic nucleotide phosphodiesterases PDE3 and PDE4, whereas IL-3, granulocyte-macrophage CSF

48 of a novel inhaled dual phosphodiesterase 3 (PDE3) and PDE4 inhibitor, RPL554 for its ability to act

49 ce regulator (CFTR) -driven fluid secretion (PDE3), and response to vasopressin V2 receptor activatio

50 d multiple phosphodiesterase isoforms (PDE2, PDE3, and PDE4).

51 hostins were also potent inhibitors of PDE1, PDE3, and PDE4.

52 a methoxy group raised the IC(50) for PDE1, PDE3, and PDE4.

53 Importantly, inhibition of PDE3, and thus perturbation of the spatiotemporal regula

54 A activity and identify phosphodiesterase 3 (PDE3) as a critical regulator in maintaining this spatia

55 creatic islets, inhibition of both PDE1C and PDE3 augmented glucose-dependent insulin secretion.

56 ibited cAMP-hydrolyzing phosphodiesterase 3 (PDE3) blocked SNAP- and CNP-elicited effects on NF-kappa

57 ltured cardiomyocytes, chronic inhibition of PDE3 but not PDE4 activity by pharmacological agents or

58 structure increased the potency for PDE1 and PDE3, but not PDE4.

59 F) or PKC (PMA), but selective activation of PDE3 by IL-4 is MAP kinase independent (but perhaps IRS-

60 The N-terminal portion of PDE3 can be arbitrarily divided into region 1 (aa 1-300)

61 ial and harmful effects, and, if so, whether PDE3 can be targeted so as to increase contractility wit

62 Three isoforms of PDE3 (cGMP-inhibited) cyclic nucleotide phosphodiesteras

63 Specific PDE3 (cilostamide) and PDE4 (rolipram) inhibitors suppre

64 ut not by specific inhibitors of the PDE1 or PDE3 classes.

65 ic activity in microsomal fractions, whereas PDE3 constitutes the majority of cAMP hydrolytic activit

66 ounts of N-terminal sequence, aggregation of PDE3 decreased, and H3A-Delta607, H3A-Delta721, and M3B-

67 cellular compartments of human myocardium by PDE3-dependent and PDE3-independent mechanisms.

68 trophy after transverse aortic constriction, PDE3 effects were not affected, whereas the contribution

69 In particular, PDE3 enzymes play a major role in regulating cAMP metabo

70 ents with heart failure, the contribution of PDE3 expression/activity in heart failure is not well kn

71 The PDE3 family comprises two highly homologous subtypes exp

72 ICa-L after the cGMP-inhibited PDE isozyme (PDE3) had been selectively inhibited by milrinone (5 mum

73 lectively activates PKG but does not inhibit PDE3, had no effect on NF-kappaB-mediated transcription.

74 resented by compound 4c: PDE1, IC50 = 60 nM; PDE3, IC50 = 55,000 nM; PDE5, IC50 = 75 nM.

75 e supported a switching from cGMP acting via PDE3 in control neurons to PDE2A in SHR neurons in the m

76 ts of human myocardium by PDE3-dependent and PDE3-independent mechanisms.

77 and SERCA2 activity; this was potentiated by PDE3 inhibition but not by PDE4 inhibition.

78 Furthermore, PDE3 inhibition had no effect on PDE3A(-/-) hearts but i

79 ments of human myocardium and the effects of PDE3 inhibition on cAMP hydrolysis in these compartments

80 very useful tool to evaluate the effects of PDE3 inhibition on lipolysis and metabolic rate and migh

81 These results indicate that PDE3 inhibition regulates endothelial CD39 at a post-tra

82 39 mRNA and protein were both elevated after PDE3 inhibition.

83 l was displaced to the left by PDE4, but not PDE3, inhibition.

84 enoceptor stimulation of brown adipocytes, a PDE3 inhibitor alone could potentiate induction of UCP1

85 e apoptotic protein BAD was inhibited by the PDE3 inhibitor cilostamide.

86 The PDE3 inhibitor, cilostamide, showed especially strong cG

87 to -5 inhibitors revealed that the specific PDE3 inhibitor, milrinone, accelerated spontaneous firin

88 ipram, but not the cAMP phosphodiesterase-3 (PDE3) inhibitor cilostamide, causes profound growth arre

89 und that cilostamide, a phosphodiesterase 3 (PDE3) inhibitor, (i) reversed the established effects of

90 Whereas PDE3 inhibitors alone had no effect, the combination of

91 ISO and PDE3 inhibitors also induced the PDE3A-ICER feedback loo

92 es cAMP-mediated signaling in the heart, and PDE3 inhibitors augment contractility in patients with h

93 Molecular models show that the PDE3 inhibitors cilostazol and milrinone share some of c

94 thelial cells (HUVECs) were treated with the PDE3 inhibitors cilostazol and milrinone, then analyzed

95 The combination of PDE4 and PDE3 inhibitors expresses synergistic effects and may br

96 PDE3 inhibitors have been used to 'overcome' the reducti

97 Although chronic treatment with PDE3 inhibitors increases mortality in patients with hea

98 chniques we analyzed the effects of PDE4 and PDE3 inhibitors on human immune cells to address these d

99 lls and was inhibited to a greater extent by PDE3 inhibitors than by rolipram, a PDE4 inhibitor.

100 PDE3 inhibitors, by raising cAMP content, have acute ino

101 of PDE4, rolipram and denbufylline, whereas PDE3 inhibitors, cilostamide and lixazinone, had no effe

102 Phosphodiesterase III (PDE3) inhibitors are inotropic agents used to treat cong

103 Therefore, PDE3 is a novel mediator of inflammation in VSMCs.

104 yte and that regulation of the activity of a PDE3 is a step distal to the kinase activation.

105 Cyclic nucleotide phosphodiesterase 3 (PDE3) is an important regulator of cyclic adenosine mono

106 e findings indicate that the contribution of PDE3 isoforms to the regulation of cAMP hydrolysis in in

107 ort the conclusion that PDE3A is the primary PDE3 isozyme modulating basal contractility and SR Ca(2+

108 KD, we examined cyst development in Pde1- or Pde3-knockout mice on the Pkd2(-/WS25) background (WS25

109 Xenopus oocytes and rescues the phenotype of pde3(-/-) mouse oocytes.

110 reverse transcription-PCR indicated that TCC PDE3 mRNA was of the PDE3B, not PDE3A, subtype.

111 seases, It is now recognised that the use of PDE3, PDE4 and mixed PDE3/4 inhibitors can provide clini

112 +)/calmodulin-activated (PDE1) and other non-PDE3 phosphodiesterases reduces their contribution to <2

113 n the dual cAMP/cGMP binding capabilities of PDE3, provide the molecular basis for inhibitor specific

114 Cyclic nucleotide phosphodiesterase 3A (PDE3) regulates cAMP-mediated signaling in the heart, an

115 lex with a generic PDE inhibitor and a novel PDE3 selective inhibitor.

116 3-isobutyl-1-methylxanthine (IBMX), and the PDE3 selective inhibitors milrinone and cilostazol each

117 To identify amino acid residues involved in PDE3-selective inhibitor binding, we selected eight pres

118 h these results, inhibitors of PDE4, but not PDE3, selectively abolished the lateral confinement of c

119 cAMP-dependent transcription, inhibitors of PDE3 (siguazodan, cilostazol) and PDE4 (rolipram, GSK256

120 pecific (74.6+/-13.8 pmol/mg per minute) and PDE3-specific (48.2+/-15.9 pmol/mg per minute) activitie

121 In addition, total PDE- and PDE3-specific activities were not altered in pediatric I

122 r specific for the type 3 phosphodiesterase (PDE3), suggesting that the activity of a PDE is required

123 tion, after natriuretic peptide stimulation, PDE3 was also involved in cGMP/cAMP crosstalk.

124 Ca,L)) by approximately 46%, indicating that PDE3 was the major constitutively active PDE in the basa

125 vely activated MEK, MAP kinase and PDE4, not PDE3, were activated.

126 tes mitogenesis is determined by activity of PDE3, whereas another cAMP-PKA pathway is directed by ac

127 ctive or only weakly active as inhibitors of PDE3, which is a major isozyme involved in cAMP hydrolys

128 al determinants important for association of PDE3 with intracellular membranes, as well for self-asso