cGMP becomes a drug target

• Published in: Naunyn-Schmiedeberg's archives of pharmacology Vol. 385; no. 3; pp. 243 - 252
• Main Authors: Schlossmann, Jens, Schinner, Elisabeth
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.03.2012
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - physiopathology; Cyclic GMP - metabolism; Drug Design; Guanylate Cyclase - metabolism; Humans; Hypertension, Pulmonary - drug therapy; Hypertension, Pulmonary - physiopathology; Molecular Targeted Therapy; Neurosciences; Pharmacology/Toxicology; Receptors, Cytoplasmic and Nuclear - metabolism; Review; Signal Transduction - drug effects; Soluble Guanylyl Cyclase; Guanylyl cyclases; cGMP-dependent protein kinase; sGC stimulator; Guanylate cyclases; cGMP; sGC activator; Pulmonary hypertension; Natriuretic peptides
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-012-0730-6

Cyclic guanosine 3′,5′-monophosphate (cGMP) serves as a second messenger molecule, which regulates pleiotropic cellular functions in health and disease. cGMP is generated by particulate or soluble guanylyl cyclases upon stimulation with natriuretic peptides or nitric oxide, respectively. Furthermore, the cGMP concentration is modulated by cGMP-degrading phosphodiesterases. Several targets of cGMP are utilized to effect its various cellular functions. These effector molecules comprise cGMP-dependent protein kinases, ion channels, and phosphodiesterases. During the last decade, it emerged that cGMP is a novel drug target for the treatment of pulmonary and cardiovascular disorders. In this respect, several drugs were developed, which are now in clinical phase studies for, e.g., pulmonary hypertension or cardiovascular diseases. These new drugs act NO-independently with/without heme on soluble guanylyl cyclases or induce subtypes of particular guanylyl cyclases and thereby lead to new therapeutic concepts and horizons. In this regard, the fifth cGMP meeting held in June 2011 in Halle, Germany, comprised the new therapeutic challenges with the novel functional and structural concepts of cGMP generating and effector molecules. This report summarizes the new data on molecular mechanisms, (patho)physiological relevance, and therapeutic potentials of the cGMP signaling system that were presented at this meeting.