Nitric Oxide and Cyclic GMP Signaling Pathway as a Focus for Drug Development

Abstract

Recent progress in understanding of the nitric oxide and cGMP signaling pathway provided evidence for mechanism of action of known drugs and identified novel targets for drug development. These discoveries resulted in numerous efforts in drug and formulation discovery. Some of the most promising approaches were applied for efficient therapies of various diseases.

Nitric Oxide and Heat Shock Protein 90 Activate Soluble Guanylate Cyclase by Driving Rapid Change in Its Subunit Interactions and Heme Content

“…Although the sGC heme normally functions in its reduced (ferrous) oxidation state, an increase in cell oxidant stress that can occur under many inflammatory conditions (7) can cause oxidation and loss of the sGC heme, thus creating a population of heme-free (apo) sGC that is insensitive to NO (8,9). This led to development of novel drug candidates that can activate sGC independent of NO or its heme (10,11) and has piqued interest in the cellular mechanisms that control the heme content, protein associations, and activity of sGC.…”

Blockade of nitric oxide synthesis stimulates the activity of adrenal cortex

“…Azot-monoksid učestvuje u regulaciji različitih bioloških procesa u organizmu. Mehanizmi delovanja NO obuhvataju: aktivaciju solubilne gvanilat ciklaze i stvaranje cikličnog guanozin-monofosfata, vezivanje sa hem grupama u drugim enzimima, formiranje peroksinitritnog anjona u reakciji sa superoksidnim anjonom, i nitrozilaciju proteina, lipida i nukleinskih kiselina (3,4 …”

“…Azot-monoksid učestvuje u regulaciji različitih bioloških procesa u organizmu. Mehanizmi delovanja NO obuhvataju: aktivaciju solubilne gvanilat ciklaze i stvaranje cikličnog guanozin-monofosfata, vezivanje sa hem grupama u drugim enzimima, formiranje peroksinitritnog anjona u reakciji sa superoksidnim anjonom, i nitrozilaciju proteina, lipida i nukleinskih kiselina (3,4 Nadbuburežna žlezda kao deo hipotalamo-hipofiznonadbubrežne (HPA) osovine i simpatoadrenalnog sistema reguliše odgovor organizma na različite stresore. Nervni impulsi, hormonsko i citokinsko delovanje integrišu se na nivou hipotalamusa odakle se putem kortikotropin oslobađajućeg hormona i arginin-vasopresina utiče na aktivnost adenohipofize.…”

Structure/Activity Relationships of (M)ANT- and TNP-Nucleotides for Inhibition of Rat Soluble Guanylyl Cyclase α1β1

“…Soluble guanylyl cyclase (sGC) is activated by nitric oxide (NO) and plays an important role in the regulation of cardiovascular and neuronal functions (Friebe and Koesling, 2009;Kots et al, 2011;Derbyshire and Marletta, 2012). Binding of NO to the heme moiety of the enzyme induces a conformational change so that sGC then effectively catalyzes the conversion of GTP into the second messenger cGMP (Friebe and Koesling, 2009;Kots et al, 2011;Derbyshire and Marletta, 2012).…”

“…Binding of NO to the heme moiety of the enzyme induces a conformational change so that sGC then effectively catalyzes the conversion of GTP into the second messenger cGMP (Friebe and Koesling, 2009;Kots et al, 2011;Derbyshire and Marletta, 2012). NO-containing drugs are used clinically to improve symptoms in coronary heart disease (Daiber et al, 2010).…”