Редактирование: PDE5A

cGMP-specific 3',5'-cyclic phosphodiesterase (EC 3.1.4.35) (cGMP-binding cGMP-specific phosphodiesterase) (CGB-PDE) [PDE5]

==Publications==

{{medline-entry
|title=Repurposing erectile dysfunction drugs tadalafil and vardenafil to increase bone mass.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32513693
|abstract=We report that two widely-used drugs for erectile dysfunction, tadalafil and vardenafil, trigger bone gain in mice through a combination of anabolic and antiresorptive actions on the skeleton. Both drugs were found to enhance osteoblastic bone formation in vivo using a unique gene footprint and to inhibit osteoclast formation. The target enzyme, phosphodiesterase 5A ([[PDE5A]]), was found to be expressed in mouse and human bone as well as in specific brain regions, namely the locus coeruleus, raphe pallidus, and paraventricular nucleus of the hypothalamus. Localization of [[PDE5A]] in sympathetic neurons was confirmed by coimmunolabeling with dopamine β-hydroxylase, as well as by retrograde bone-brain tracing using a sympathetic nerve-specific pseudorabies virus, PRV152. Both drugs elicited an antianabolic sympathetic imprint in osteoblasts, but with net bone gain. Unlike in humans, in whom vardenafil is more potent than tadalafil, the relative potencies were reversed with respect to their osteoprotective actions in mice. Structural modeling revealed a higher binding energy of tadalafil to mouse [[PDE5A]] compared with vardenafil, due to steric clashes of vardenafil with a single methionine residue at position 806 in mouse [[PDE5A]]. Collectively, our findings suggest that a balance between peripheral and central actions of [[PDE5A]] inhibitors on bone formation together with their antiresorptive actions specify the osteoprotective action of [[PDE5A]] blockade.
|mesh-terms=* Aging
* Animals
* Bone Density
* Bone and Bones
* Brain
* Cell Differentiation
* Cyclic Nucleotide Phosphodiesterases, Type 5
* Drug Repositioning
* Erectile Dysfunction
* Humans
* Male
* Mice
* Middle Aged
* Models, Animal
* Models, Molecular
* Neurons
* Osteoblasts
* Osteoclasts
* Osteogenesis
* Osteoporosis
* Osteoporotic Fractures
* Phosphodiesterase 5 Inhibitors
* Primary Cell Culture
* Tadalafil
* Vardenafil Dihydrochloride
|keywords=* PDE5 inhibitor
* computational modeling
* cyclic GMP
* osteoporosis
* resorption
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321982
}}
{{medline-entry
|title=Select 3',5'-cyclic nucleotide phosphodiesterases exhibit altered expression in the aged rodent brain.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24184653
|abstract=3',5'-cyclic nucleotide phosphodiesterases (PDEs) are the only known enzymes to compartmentalize cAMP and cGMP, yet little is known about how PDEs are dynamically regulated across the lifespan. We mapped mRNA expression of all 21 PDE isoforms in the adult rat and mouse central nervous system (CNS) using quantitative polymerase chain reaction (qPCR) and in situ hybridization to assess conservation across species. We also compared PDE mRNA and protein in the brains of old (26 months) versus young (5 months) Sprague-Dawley rats, with select experiments replicated in old (9 months) versus young (2 months) BALB/cJ mice. We show that each PDE isoform exhibits a unique expression pattern across the brain that is highly conserved between rats, mice, and humans. [[PDE1B]], [[PDE1C]], [[PDE2A]], [[PDE4A]], [[PDE4D]], [[PDE5A]], [[PDE7A]], [[PDE8A]], [[PDE8B]], [[PDE10A]], and [[PDE11A]] showed an age-related increase or decrease in mRNA expression in at least 1 of the 4 brain regions examined (hippocampus, cortex, striatum, and cerebellum). In contrast, mRNA expression of [[PDE1A]], [[PDE3A]], [[PDE3B]], [[PDE4B]], [[PDE7A]], [[PDE7B]], and [[PDE9A]] did not change with age. Age-related increases in [[PDE11A]]4, [[PDE8A]]3, [[PDE8A]]4/5, and [[PDE1C]]1 protein expression were confirmed in hippocampus of old versus young rodents, as were age-related increases in [[PDE8A]]3 protein expression in the striatum. Age-related changes in PDE expression appear to have functional consequences as, relative to young rats, the hippocampi of old rats demonstrated strikingly decreased phosphorylation of GluR1, CaMKIIα, and CaMKIIβ, decreased expression of the transmembrane AMPA regulatory proteins γ2 (a.k.a. stargazin) and γ8, and increased trimethylation of H3K27. Interestingly, expression of [[PDE11A]]4, [[PDE8A]]4/5, [[PDE8A]]3, and [[PDE1C]]1 correlate with these functional endpoints in young but not old rats, suggesting that aging is not only associated with a change in PDE expression but also a change in PDE compartmentalization.
|mesh-terms=* 3',5'-Cyclic-AMP Phosphodiesterases
* Aging
* Animals
* Brain
* Cerebellum
* Cerebral Cortex
* Corpus Striatum
* Gene Expression Regulation, Enzymologic
* Hippocampus
* Male
* Mice
* Mice, Inbred BALB C
* Protein Isoforms
* RNA, Messenger
* Rats
* Rats, Sprague-Dawley
|keywords=* Alzheimer's disease
* Model
* Neuron
* PDE11
* PDE8
* Tissue distribution
|full-text-url=https://sci-hub.do/10.1016/j.cellsig.2013.10.007
}}