| http://purl.uniprot.org/citations/21187369 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21187369 | http://www.w3.org/2000/01/rdf-schema#comment | "The functions of the phosphodiesterase 8B (PDE8) family of phosphodiesterases have been largely unexplored because of the unavailability of selective pharmacological inhibitors. Here, we report a novel function of PDE8B as a major regulator of adrenal steroidogenesis using a genetically ablated PDE8B mouse model as well as cell lines treated with either a new PDE8-selective inhibitor or a short hairpin RNA (shRNA) construct against PDE8B. We demonstrate that PDE8B is highly enriched in mouse adrenal fasciculata cells, and show that PDE8B knockout mice have elevated urinary corticosterone as a result of adrenal hypersensitivity toward adrenocorticotropin. Likewise, ablation of PDE8B mRNA transcripts by an shRNA construct potentiates steroidogenesis in the commonly used Y-1 adrenal cell line. We also observed that the PDE8-selective inhibitor (PF-04957325) potentiates adrenocorticotropin stimulation of steroidogenesis by increasing cAMP-dependent protein kinase activity in both primary isolated adrenocortical cells and Y-1 cells. It is noteworthy that PDE8s have their greatest control under low adrenocorticotropin-stimulated conditions, whereas other higher K(m) PDE(s) modulate steroidogenesis more effectively when cells are fully stimulated. Finally, both genetic ablation of PDE8B and long-term pharmacological inhibition of PDE8s cause increased expression of steroidogenic enzymes. We conclude that PDE8B is a major regulator of one or more pools of cAMP that promote steroidogenesis via both short- and long-term mechanisms. These findings further suggest PDE8B as a potential therapeutic target for the treatment of several different adrenal diseases."xsd:string |
| http://purl.uniprot.org/citations/21187369 | http://purl.org/dc/terms/identifier | "doi:10.1124/mol.110.069104"xsd:string |
| http://purl.uniprot.org/citations/21187369 | http://purl.uniprot.org/core/author | "Beavo J.A."xsd:string |
| http://purl.uniprot.org/citations/21187369 | http://purl.uniprot.org/core/author | "Tsai L.C."xsd:string |
| http://purl.uniprot.org/citations/21187369 | http://purl.uniprot.org/core/author | "Shimizu-Albergine M."xsd:string |
| http://purl.uniprot.org/citations/21187369 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21187369 | http://purl.uniprot.org/core/name | "Mol Pharmacol"xsd:string |
| http://purl.uniprot.org/citations/21187369 | http://purl.uniprot.org/core/pages | "639-648"xsd:string |
| http://purl.uniprot.org/citations/21187369 | http://purl.uniprot.org/core/title | "The high-affinity cAMP-specific phosphodiesterase 8B controls steroidogenesis in the mouse adrenal gland."xsd:string |
| http://purl.uniprot.org/citations/21187369 | http://purl.uniprot.org/core/volume | "79"xsd:string |
| http://purl.uniprot.org/citations/21187369 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21187369 |
| http://purl.uniprot.org/citations/21187369 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/21187369 |
| http://purl.uniprot.org/uniprot/E9Q4S1#attribution-1F63D1F81FAAD17C044F84B6647818D6 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/21187369 |
| http://purl.uniprot.org/uniprot/E9Q4S1#attribution-C5B82F9F3E164B1DE0B3013925E783C6 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/21187369 |
| http://purl.uniprot.org/uniprot/#_E0CXQ1-mappedCitation-21187369 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21187369 |
| http://purl.uniprot.org/uniprot/#_E0CY70-mappedCitation-21187369 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21187369 |
| http://purl.uniprot.org/uniprot/#_E9Q7S6-mappedCitation-21187369 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21187369 |
| http://purl.uniprot.org/uniprot/#_A6YR19-mappedCitation-21187369 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21187369 |
| http://purl.uniprot.org/uniprot/#_F7CT85-mappedCitation-21187369 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21187369 |
| http://purl.uniprot.org/uniprot/#_E9Q8J6-mappedCitation-21187369 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21187369 |
| http://purl.uniprot.org/uniprot/#_E9PX38-mappedCitation-21187369 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21187369 |
| http://purl.uniprot.org/uniprot/#_E9Q4S1-mappedCitation-21187369 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21187369 |
| http://purl.uniprot.org/uniprot/#_E9PUL4-mappedCitation-21187369 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21187369 |
| http://purl.uniprot.org/uniprot/#_E9PXX4-mappedCitation-21187369 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21187369 |