Pde4d phosphodiesterase 4D [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Pde4dprovided by RGD
Official Full Name: phosphodiesterase 4Dprovided by RGD
Primary source: RGD:3281
See related: EnsemblRapid:ENSRNOG00000042536 AllianceGenome:RGD:3281
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: DPDE3; PDE3/IVd
Summary: Enables several functions, including beta-2 adrenergic receptor binding activity; cyclic-nucleotide phosphodiesterase activity; and signaling receptor regulator activity. Involved in several processes, including establishment of endothelial barrier; positive regulation of smooth muscle cell proliferation; and regulation of heart contraction. Located in centrosome and myofibril. Part of protein-containing complex. Used to study depressive disorder. Biomarker of transient cerebral ischemia. Human ortholog(s) of this gene implicated in acrodysostosis. Orthologous to human PDE4D (phosphodiesterase 4D). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Biased expression in Muscle (RPKM 125.3), Thymus (RPKM 97.1) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 2q14

Exon count:: 36

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	2	NC_086020.1 (41748337..43262567)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	2	NC_051337.1 (40014933..41529190)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	2	NC_005101.4 (40219999..41468551)

Chromosome 2 - NC_086020.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Targeting Aquaporin-5 by Phosphodiesterase 4 Inhibition Offers New Therapeutic Opportunities for Ovarian Ischemia Reperfusion Injury in Rats.
Title: Targeting Aquaporin-5 by Phosphodiesterase 4 Inhibition Offers New Therapeutic Opportunities for Ovarian Ischemia Reperfusion Injury in Rats.
Overexpression of Pde4d in rat granulosa cells inhibits maturation and atresia of antral follicles to induce polycystic ovary.
Title: Overexpression of Pde4d in rat granulosa cells inhibits maturation and atresia of antral follicles to induce polycystic ovary.
Cold-Inducible RNA-Binding Protein Prevents an Excessive Heart Rate Response to Stress by Targeting Phosphodiesterase.
Title: Cold-Inducible RNA-Binding Protein Prevents an Excessive Heart Rate Response to Stress by Targeting Phosphodiesterase.
The mRNA expression of PDE4D was significantly increased in allergic rats, but PDE4B was not. PDE4B was mainly distributed in the cytoplasm, whereas PDE4D was mainly distributed in the cell membrane
Title: Anti‑inflammatory effect of ciclamilast in an allergic model involving the expression of PDE4B.
Data reveal essential roles of beta-arrestin 2 and PDE4D in a common mechanism for heterologous desensitization of cardiac beta adrenergic receptors under hormonal stimulation, which is associated with impaired cardiac function during the development of pathophysiological conditions.
Title: Heterologous desensitization of cardiac β-adrenergic signal via hormone-induced βAR/arrestin/PDE4 complexes.
SIK1 serves as a part of a self-regulatory circuit to modulate insulin secretion from pancreatic beta-cells by controlling cAMP concentration through modulation of PDE4D activity.
Title: Salt-Inducible Kinase 1 Terminates cAMP Signaling by an Evolutionarily Conserved Negative-Feedback Loop in β-Cells.
specific inhibitory PDE4D mutations can lead to the molecular pathology of acrodysostosis without hormone resistance but that the pathological phenotype may well be dependent on an over-compensatory induction of other PDE4 isoforms
Title: Heterozygous mutations in cyclic AMP phosphodiesterase-4D (PDE4D) and protein kinase A (PKA) provide new insights into the molecular pathology of acrodysostosis.
PDE4D9 was found to locate primarily not only in the perinuclear region of Rat-1 cells but also at the cell margins.
Title: Mitotic activation of the DISC1-inducible cyclic AMP phosphodiesterase-4D9 (PDE4D9), through multi-site phosphorylation, influences cell cycle progression.
Inhibition of PDE4D activity decreases hepatic inflammation, injury and fibrosis.
Title: Rolipram attenuates bile duct ligation-induced liver injury in rats: a potential pathogenic role of PDE4.
The effect of increased PDE4D expression following cerebral ischemia may play a role in changing blood-brain barrier permeability, which could secondarily affect ischemic outcome.
Title: Ischemia-induced increase in microvascular phosphodiesterase 4D expression in rat hippocampus associated with blood brain barrier permeability: effect of age.

Submit: New GeneRIF Correction See all GeneRIFs (22)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D2Rat199 (e-PCR), detects polymorphism
- UniSTS:227359

RH138883 (e-PCR)
- UniSTS:220970

AU049525 (e-PCR)
- UniSTS:145972

BQ192875 (e-PCR)
- UniSTS:261703

D2Got25 (e-PCR)
- UniSTS:115016

D2Mco27 (e-PCR)
- UniSTS:239448

D2Rat317 (e-PCR)
- UniSTS:239704

fb98c02.x1 (e-PCR)
- UniSTS:203609

AA955553 (e-PCR)
- UniSTS:246657

AU046382 (e-PCR)
- UniSTS:111494

D2Rat18 (e-PCR)
- UniSTS:118678

13.MMHAP86FRE7.seq (e-PCR)
- UniSTS:186310

BF401594 (e-PCR)
- UniSTS:261352

BF403774 (e-PCR)
- UniSTS:246513

Pde4d (e-PCR), detects polymorphism
- UniSTS:507124

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables 3',5'-cyclic-AMP phosphodiesterase activity	IBA Inferred from Biological aspect of Ancestor more info
enables 3',5'-cyclic-AMP phosphodiesterase activity	IEA Inferred from Electronic Annotation more info
enables 3',5'-cyclic-AMP phosphodiesterase activity	ISO Inferred from Sequence Orthology more info
enables 3',5'-cyclic-GMP phosphodiesterase activity	IBA Inferred from Biological aspect of Ancestor more info
enables 3',5'-cyclic-nucleotide phosphodiesterase activity	IEA Inferred from Electronic Annotation more info
enables 3',5'-cyclic-nucleotide phosphodiesterase activity	ISO Inferred from Sequence Orthology more info
enables ATPase binding	IEA Inferred from Electronic Annotation more info
enables ATPase binding	ISO Inferred from Sequence Orthology more info
enables beta-2 adrenergic receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables cAMP binding	IEA Inferred from Electronic Annotation more info
enables cAMP binding	ISO Inferred from Sequence Orthology more info
enables calcium channel regulator activity	ISO Inferred from Sequence Orthology more info
enables cyclic-nucleotide phosphodiesterase activity	IDA Inferred from Direct Assay more info	PubMed
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables heterocyclic compound binding	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables scaffold protein binding	IEA Inferred from Electronic Annotation more info
enables scaffold protein binding	ISO Inferred from Sequence Orthology more info
enables signaling receptor regulator activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables transmembrane transporter binding	IEA Inferred from Electronic Annotation more info
enables transmembrane transporter binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in T cell receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in T cell receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in adrenergic receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cAMP catabolic process	IEA Inferred from Electronic Annotation more info
involved_in cAMP-mediated signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in cAMP/PKA signal transduction	ISO Inferred from Sequence Orthology more info
involved_in cellular response to cAMP	ISO Inferred from Sequence Orthology more info
involved_in cellular response to epinephrine stimulus	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cellular response to follicle-stimulating hormone stimulus	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cellular response to lipopolysaccharide	ISO Inferred from Sequence Orthology more info
involved_in establishment of endothelial barrier	IDA Inferred from Direct Assay more info	PubMed
involved_in lung development	IEP Inferred from Expression Pattern more info	PubMed
involved_in memory	IEP Inferred from Expression Pattern more info	PubMed
involved_in memory	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within multicellular organism growth	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of heart contraction	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of peptidyl-serine phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of relaxation of cardiac muscle	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within neutrophil chemotaxis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within neutrophil migration	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within ovulation from ovarian follicle	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell-cell adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of heart rate	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interleukin-2 production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of interleukin-2 production	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of interleukin-5 production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of interleukin-5 production	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of smooth muscle cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of smooth muscle cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of type II interferon production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of type II interferon production	ISO Inferred from Sequence Orthology more info
involved_in protein-containing complex assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cAMP/PKA signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of calcium ion transmembrane transport via high voltage-gated calcium channel	ISO Inferred from Sequence Orthology more info
involved_in regulation of cardiac muscle cell contraction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cardiac muscle cell contraction	ISO Inferred from Sequence Orthology more info
involved_in regulation of cell communication by electrical coupling involved in cardiac conduction	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell communication by electrical coupling involved in cardiac conduction	ISO Inferred from Sequence Orthology more info
involved_in regulation of heart rate	ISO Inferred from Sequence Orthology more info
involved_in regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	ISO Inferred from Sequence Orthology more info
involved_in signal transduction	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within smooth muscle contraction	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
part_of calcium channel complex	IEA Inferred from Electronic Annotation more info
part_of calcium channel complex	ISO Inferred from Sequence Orthology more info
located_in centrosome	IDA Inferred from Direct Assay more info	PubMed
located_in centrosome	ISO Inferred from Sequence Orthology more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
NOT located_in membrane	ISO Inferred from Sequence Orthology more info
located_in membrane	ISO Inferred from Sequence Orthology more info
located_in myofibril	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
part_of potassium channel complex	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
part_of voltage-gated calcium channel complex	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: 3',5'-cyclic-AMP phosphodiesterase 4D

Names: 3',5'-cyclic AMP phosphodiesterase; cAMP-specific 3',5'-cyclic phosphodiesterase 4D; cAMP-specific phosphodiesterase 4D; cAMP-specific phosphodiesterase PDE4D; phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, Drosophila)

NP_001106799.1

EC 3.1.4.53

NP_001106800.1

EC 3.1.4.53

NP_001106803.1

EC 3.1.4.53

NP_001106805.1

EC 3.1.4.53

NP_058728.1

EC 3.1.4.53

XP_008758943.1

EC 3.1.4.53

XP_008758944.1

EC 3.1.4.53

XP_008758945.1

EC 3.1.4.53

XP_038957661.1

EC 3.1.4.53

XP_038957664.1

EC 3.1.4.53

XP_038957665.2

EC 3.1.4.53

XP_038957667.1

EC 3.1.4.53

XP_063137368.1

EC 3.1.4.53

XP_063137369.1

EC 3.1.4.53

XP_063137370.1

EC 3.1.4.53

XP_063137371.1

EC 3.1.4.53

XP_063137372.1

EC 3.1.4.53

XP_063137373.1

EC 3.1.4.53

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001113328.2 → NP_001106799.1 3',5'-cyclic-AMP phosphodiesterase 4D isoform 1

See identical proteins and their annotated locations for NP_001106799.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

JAXUCZ010000002

UniProtKB/Swiss-Prot

A1E347, A1EC59, F1M1H7, O35470, P14270, Q6TRI0, Q8CG04, Q8CG06

UniProtKB/TrEMBL

A0A8I6ABM9, A6I5L1

Related

ENSRNOP00000090781.1, ENSRNOT00000112415.2

Conserved Domains (1) summary

pfam00233
Location:456 → 697

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
NM_001113329.2 → NP_001106800.1 3',5'-cyclic-AMP phosphodiesterase 4D isoform 2

See identical proteins and their annotated locations for NP_001106800.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) has an alternate 5' coding sequence including two exons, as compared to variant 1. The resulting isoform (2) has a shorter N-terminus, as compared to isoform 1.

Source sequence(s)

JAXUCZ010000002

UniProtKB/TrEMBL

A6I5K8, A6I5L0

Conserved Domains (2) summary

pfam00233
Location:400 → 641

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

pfam18100
Location:162 → 278

PDE4_UCR; Phosphodiesterase 4 upstream conserved regions (UCR)
NM_001113332.2 → NP_001106803.1 3',5'-cyclic-AMP phosphodiesterase 4D isoform 3

See identical proteins and their annotated locations for NP_001106803.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) has an alternate 5' coding exon, as compared to variant 1. The resulting isoform (3) has a shorter N-terminus, as compared to isoform 1.

Source sequence(s)

JAXUCZ010000002

UniProtKB/TrEMBL

A6I5L2

Related

ENSRNOP00000093090.1, ENSRNOT00000113369.2

Conserved Domains (1) summary

pfam00233
Location:398 → 639

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
NM_001113334.2 → NP_001106805.1 3',5'-cyclic-AMP phosphodiesterase 4D isoform 4

See identical proteins and their annotated locations for NP_001106805.1

Status: VALIDATED

Description

Transcript Variant: This variant (4) has an alternate 5' coding exon, as compared to variant 1. The resulting isoform (4) has a shorter N-terminus, as compared to isoform 1.

Source sequence(s)

JAXUCZ010000002

UniProtKB/TrEMBL

A6I5L2

Related

ENSRNOP00000094176.2, ENSRNOT00000111781.2

Conserved Domains (1) summary

pfam00233
Location:339 → 580

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
NM_017032.2 → NP_058728.1 3',5'-cyclic-AMP phosphodiesterase 4D isoform 5

See identical proteins and their annotated locations for NP_058728.1

Status: VALIDATED

Description

Transcript Variant: This variant (5) has an alternate 5' coding exon, as compared to variant 1. The resulting isoform (5) has a shorter N-terminus, as compared to isoform 1.

Source sequence(s)

JAXUCZ010000002

UniProtKB/TrEMBL

A0A8I6A4N5, A6I5L4

Related

ENSRNOP00000086862.1, ENSRNOT00000112056.2

Conserved Domains (1) summary

pfam00233
Location:325 → 566

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCr8

Genomic

NC_086020.1 Reference GRCr8

Range

41748337..43262567

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_039101733.2 → XP_038957661.1 3',5'-cyclic-AMP phosphodiesterase 4D isoform X1

UniProtKB/TrEMBL

A6I5K8, A6I5L0

Conserved Domains (2) summary

pfam00233
Location:400 → 641

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

pfam18100
Location:162 → 278

PDE4_UCR; Phosphodiesterase 4 upstream conserved regions (UCR)
XM_063281298.1 → XP_063137368.1 3',5'-cyclic-AMP phosphodiesterase 4D isoform X1

UniProtKB/TrEMBL

A6I5K8
XM_063281299.1 → XP_063137369.1 3',5'-cyclic-AMP phosphodiesterase 4D isoform X1

UniProtKB/TrEMBL

A6I5K8
XM_063281301.1 → XP_063137371.1 3',5'-cyclic-AMP phosphodiesterase 4D isoform X1

UniProtKB/TrEMBL

A6I5K8
XM_063281300.1 → XP_063137370.1 3',5'-cyclic-AMP phosphodiesterase 4D isoform X1

UniProtKB/TrEMBL

A6I5K8
XM_063281302.1 → XP_063137372.1 3',5'-cyclic-AMP phosphodiesterase 4D isoform X1

UniProtKB/TrEMBL

A6I5K8

Related

ENSRNOP00000076534.1, ENSRNOT00000110594.2
XM_039101736.2 → XP_038957664.1 3',5'-cyclic-AMP phosphodiesterase 4D isoform X2

UniProtKB/TrEMBL

A0A140TAB1, A6I5L2

Related

ENSRNOP00000015138.8, ENSRNOT00000015138.10

Conserved Domains (2) summary

pfam00233
Location:351 → 592

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

pfam18100
Location:113 → 229

PDE4_UCR; Phosphodiesterase 4 upstream conserved regions (UCR)
XM_008760721.3 → XP_008758943.1 3',5'-cyclic-AMP phosphodiesterase 4D isoform X3

See identical proteins and their annotated locations for XP_008758943.1

UniProtKB/TrEMBL

A6I5L5, A6I5L6

Related

ENSRNOP00000063446.3, ENSRNOT00000066384.6

Conserved Domains (1) summary

pfam00233
Location:331 → 572

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
XM_008760723.3 → XP_008758945.1 3',5'-cyclic-AMP phosphodiesterase 4D isoform X6

See identical proteins and their annotated locations for XP_008758945.1

UniProtKB/TrEMBL

A6I5L7, A6I5L8

Conserved Domains (1) summary

pfam00233
Location:159 → 400

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
XM_039101739.2 → XP_038957667.1 3',5'-cyclic-AMP phosphodiesterase 4D isoform X7

UniProtKB/TrEMBL

A0A8I6GB00, A6I5L7

Related

ENSRNOP00000083636.1, ENSRNOT00000101684.2

Conserved Domains (2) summary

pfam00233
Location:157 → 398

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

pfam18100
Location:2 → 35

PDE4_UCR; Phosphodiesterase 4 upstream conserved regions (UCR)
XM_063281303.1 → XP_063137373.1 3',5'-cyclic-AMP phosphodiesterase 4D isoform X7

UniProtKB/TrEMBL

A0A8I6GB00
XM_039101737.2 → XP_038957665.2 3',5'-cyclic-AMP phosphodiesterase 4D isoform X4
XM_008760722.4 → XP_008758944.1 3',5'-cyclic-AMP phosphodiesterase 4D isoform X5

See identical proteins and their annotated locations for XP_008758944.1

UniProtKB/TrEMBL

A6I5L7, A6I5L9

Related

ENSRNOP00000062384.2, ENSRNOT00000067546.5

Conserved Domains (1) summary

pfam00233
Location:170 → 411

PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase