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Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
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Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
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Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
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Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
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The lungs are a pair of vital organs connected to the trachea via the left and right bronchi. The base of these organs meets the dome-shaped muscle known as the diaphragm. Encased by the pleurae, the lungs contact the mediastinum. The right lung is shorter yet wider, and has a larger volume than the left lung. The left lung has an indentation known as the cardiac notch. The superior region of the lungs is referred to as the apex, whereas the base is the lower region near the diaphragm. The...
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Utilizing the Precision-Cut Lung Slice to Study the Contractile Regulation of Airway and Intrapulmonary Arterial Smooth Muscle
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NO-sensitive guanylyl cyclase in the lung.

Andreas Friebe1, Nils Englert1

  • 1Physiological Institute, Julius Maximilian University of Würzburg, Würzburg, Germany.

British Journal of Pharmacology
|December 17, 2020
PubMed
Summary

Nitric oxide-sensitive guanylyl cyclase (NO-GC) is highly expressed in the lung. While NO-GC targets are used for pulmonary hypertension, its specific lung functions, particularly in pericytes, require further elucidation.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Guanylyl cyclase (GC) produces cGMP, with two main types identified: cytosolic nitric oxide-sensitive GC (NO-GC) and membrane-bound natriuretic peptide-activated GC.
  • The lung exhibits the highest NO-GC expression among tissues, with the enzyme purified for biochemical analysis.

Purpose of the Study:

  • To investigate the function of NO-GC in lung, particularly within smooth muscle cells (SMCs) and pericytes.
  • To highlight the therapeutic potential of NO-GC targeting in various respiratory diseases.

Main Methods:

  • Biochemical analysis of purified NO-GC from lung tissue.
  • Review of existing literature on NO-GC function and therapeutic applications.

Main Results:

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  • NO-GC is highly expressed in the lung, particularly in SMCs and pericytes.
  • Pharmacological NO-GC targeting is established for pulmonary arterial hypertension therapy.
  • NO-GC is a potential therapeutic target for asthma, acute respiratory distress syndrome, and pulmonary fibrosis.

Conclusions:

  • Further research is needed to fully elucidate the function of NO-GC in lung pericytes.
  • NO-GC represents a promising drug target for managing severe lung conditions.