High lung PDE5: A strong basis for treating pulmonary hypertension with PDE5 inhibitors
| Autor: | Alfreda Beasley, Jackie D. Corbin, Mitsi A. Blount, Sharron H. Francis |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
Vascular smooth muscle Hypertension Pulmonary Biophysics Tritium Biochemistry Piperazines Tadalafil Vardenafil Dihydrochloride 3' 5'-Cyclic-GMP Phosphodiesterases In vivo Internal medicine Cyclic GMP-Dependent Protein Kinases medicine Animals Humans Sulfones Enzyme Inhibitors Phosphodiesterase inhibitor Lung Molecular Biology Cyclic Nucleotide Phosphodiesterases Type 5 Triazines Chemistry Myocardium Imidazoles Cell Biology medicine.disease Cyclic AMP-Dependent Protein Kinases Pulmonary hypertension Rats Endocrinology medicine.anatomical_structure Vardenafil Chromatography Gel cGMP-dependent protein kinase Carbolines medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 334:930-938 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2005.06.183 |
| Popis: | [3H]Vardenafil (Levitra) or [3H]tadalafil (Cialis) binding was used to quantify PDE5 in rat lung and heart tissue. Each radioligand bound to purified recombinant phosphodiesterase-5 (PDE5) or to PDE5 in crude extracts with strong affinity, high specificity, slow dissociation, and good stoichiometry. PDE5, the only 3H inhibitor-binding protein detected in extracts, was 15 times higher in lung than in heart extracts, and the level measured by PDE5 catalytic activity agreed with that determined by 3H inhibitor binding. High level of PDE5 in lung approximated that in penile corpus cavernosum, the tissue targeted by PDE5 inhibitors. PDE5 was the predominant cGMP-PDE in lung, and on a molar basis was five times higher than cGMP-dependent protein kinase (PKG), which phosphorylates PDE5 in vivo. The PDE5 level was one-half that of PKG in heart. Thus, abundance of PDE5 in lung vascular smooth muscle provides a strong molecular basis for PDE5 inhibitor treatment of pulmonary hypertension. |
| Databáze: | OpenAIRE |
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