NO‐sensitive guanylyl cyclase in the lung

Abstract

In the late 1960s, several labatories identified guanylyl cyclase (GC) as the cGMP‐producing enzyme. Subsequently, two different types of GC were described that differed in their cellular localization. Primarily found in the cytosol, nitric oxide (NO)‐sensitive guanylyl cyclase (NO‐GC) acts as receptor for the signalling molecule NO, in contrast the membrane‐bound isoenzyme is activated by natriuretic peptides. The lung compared with other tissues exhibits the highest expression of NO‐GC. The enzyme has been purified from lung for biochemical analysis. Although expressed in smooth muscle cells (SMCs) and in pericytes, the function of NO‐GC in lung, especially in pericytes, is still not fully elucidated. However, pharmacological compounds that target NO‐GC are available and have been implemented for the therapy of pulmonary arterial hypertension. In addition, NO‐GC has been suggested as drug target for the therapy of asthma, acute respiratory distress syndrome and pulmonary fibrosis. LINKED ARTICLES This article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc

GAPDH is involved in the heme‐maturation of myoglobin and hemoglobin

“…sGC activated by nitric oxide (NO) generated from NOS enzymes makes cGMP thereby constituting the NO-sGC-cGMP signal axis. 52 The generated cGMP acts as a second messenger to initiate a cascade of downstream events to cause vasodilation in the vasculature 52,64,65 or bronchodilation in the lungs. 66,67 Our current study has important biomedical relevance as it is focused on globin maturation.…”

NO in Viral Infections: Role and Development of Antiviral Therapies

“…A reduction in lung NO levels is found in diseases such as cystic fibrosis and acute respiratory distress syndrome [ 20 ]. In the lungs, NO that is produced by eNOS in endothelial cells improves oxygenation; it acts on smooth muscle cells, inducing vessel dilation and, therefore, an increase in local blood flow [ 40 ]. The main mechanism of vasodilation is the same as was described in the previous paragraph, with the involvement of sGC and cGMP.…”

“…The main mechanism of vasodilation is the same as was described in the previous paragraph, with the involvement of sGC and cGMP. A reduced sGC expression, which is related to decreased vasodilation in response to NO, is often found in adult lungs with respect to children [ 40 ]. In addition, NO acts also through cGMP-independent mechanisms: it has been reported that direct activation of Ca 2+ -dependent K + channels [ 41 ] and the involvement in the formation of nitrosothiols, which exhibit bronchodilator activity [ 42 ].…”

Recent developments in cGMP research: From mechanisms to medicines and back

“…The review section of the themed issue begins with a contribution by Friebe and Englert focusing on cGMP in the lung (Friebe & Englert, 2022). This organ expresses particularly high levels of NO‐GC, but neither the cell types expressing NO‐GC in the lung (e.g., pericytes, smooth muscle cells, and epithelial cells) nor the NO‐GC‐mediated mechanisms that affect lung physiology and pathophysiology are clear.…”

“…This British Journal of Pharmacology themed issue on cGMP signalling in cell growth and survival assembles five review articles followed by eight original research papers from leading scientists that improve our understanding of the effects of endogenous and pharmacologically modulated cGMP signals on tissue repair and maintenance. We hope that the presented insights will lead to new strategies for the management of several age-related disorders including diseases of the heart, lungs, kidneys, nervous system, and hearing organ.The review section of the themed issue begins with a contribution by Friebe and Englert focusing on cGMP in the lung (Friebe & Englert, 2022). This organ expresses particularly high levels of NO-GC, but neither the cell types expressing NO-GC in the lung (e.g., pericytes, smooth muscle cells, and epithelial cells) nor the NO-GC-mediated mechanisms that affect lung physiology and pathophysiology are clear.…”