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Role of the nitric oxide–soluble guanylyl cyclase pathway in obstructive airway diseases
- Source :
- PULMONARY PHARMACOLOGY & THERAPEUTICS
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- Nitric oxide (NO) is a gaseotransmitter, which is involved in many signaling processes in health and disease. Three enzymes generate NO from L-arginine, with citrulline formed as a by-product: neuronal NO synthase (nNOS or NOS1), endothelial NOS (eNOS or NOS3) and inducible NOS (iNOS or NOS2). NO is a ligand of soluble guanylyl cyclase (sGC), an intracellular heterodimer enzyme that catalyzes the con- version of guanosine triphosphate (GTP) to cyclic GMP (cGMP). cGMP further activates protein kinase G that eventually reduces the smooth muscle tone in bronchi or vessels. Phosphodiesterase 5 (PDE5) de- grades cGMP to GMP. However, NO reacts with superoxide anion (O � ), leading to formation of the pro- inflammatory molecule peroxynitrite. Under physiological conditions, NO plays a homeostatic bronchoprotective role in healthy subjects. In obstructive airway diseases, NO can be beneficial by its bronchodilating effect, but could also be detrimental by the formation of peroxynitrite. Since asthma and COPD are associated with increased levels of exhaled NO, chronic inflammation and increased airway smooth muscle tone, the NO/sGC/cGMP pathway could be involved in these highly prevalent obstructive airway diseases. Here we review the involvement of NO, NO synthases, guanylyl cyclases, cGMP and phophodiesterase-5 in asthma and COPD and potential therapeutic approaches to modulate this pathway.
- Subjects :
- Pulmonary and Respiratory Medicine
medicine.medical_specialty
NOS1
INHIBITION
Receptors, Cytoplasmic and Nuclear
EXHALED AIR
Nitric Oxide
Endothelial NOS
Nitric oxide
Pulmonary Disease, Chronic Obstructive
chemistry.chemical_compound
Soluble Guanylyl Cyclase
Superoxides
Soluble guanylyl cyclase
Internal medicine
Medicine and Health Sciences
PULMONARY-DISEASE
Citrulline
medicine
Animals
Humans
COPD
ALLERGIC-ASTHMA
SYNTHASE
Pharmacology (medical)
OXIDATIVE STRESS
Cyclic GMP
Cyclic Nucleotide Phosphodiesterases, Type 5
INDUCED EMPHYSEMA
HYPERTENSION
business.industry
ASTHMATIC-PATIENTS
Biochemistry (medical)
Asthma
Endocrinology
chemistry
Guanylate Cyclase
cGMP-specific phosphodiesterase type 5
Nitric Oxide Synthase
business
cGMP-dependent protein kinase
Peroxynitrite
Signal Transduction
Subjects
Details
- ISSN :
- 10945539
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Pulmonary Pharmacology & Therapeutics
- Accession number :
- edsair.doi.dedup.....6f6f19e884adcdc76729b2b534610036