cGMP-dependent protein kinases in drug discovery.
Cyclic guanosine-3', 5'-monophosphate (cGMP)-dependent protein kinases (cGKs) are key enzymes of nitric oxide-cGMP and natriuretic peptide signalling cascades. These kinases mediate most of the effects of cGMP-elevating drugs, such as nitrates and phosphodiesterase inhibitors. cGKs modulate smooth muscle relaxation (e.g. the vasculature, gastrointestinal tract, bladder and penile), platelet aggregation, renin release, intestinal secretion, learning and memory. Furthermore, several cGK substrates have been identified. Isozyme-specific inhibitors and activators of cGK and its downstream substrates might act more specifically than upstream signalling activators, such as organic nitrates and phosphodiesterase inhibitors.
Schlossmann
Jens
J
Institut für Pharmakologie und Toxikologie der Technischen Universität München, Biedersteiner Strasse 29, 80802 München, Germany. schlossmann@ipt.med.tu-muenchen.de
Hofmann
Franz
F
D000818:Animals; D001792:Blood Platelets / Q000201:enzymology; D002626:Chemistry, Pharmaceutical; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D009130:Muscle, Smooth / Q000201:enzymology; D009420:Nervous System / Q000201:enzymology; D015398:Signal Transduction
D017869:Cyclic GMP-Dependent Protein Kinases