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Related Concept Videos

Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

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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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Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
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IP3/DAG Signaling Pathway01:11

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Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
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Antihypertensive Drugs: Vasodilators01:23

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Vasodilators, primarily affecting the smooth muscles within arterial and venous walls, are commonly used for hypertension treatment. Medications such as minoxidil and hydralazine primarily target arteries and arterioles, while sodium nitroprusside acts on arterioles and venules. Minoxidil, functioning as a prodrug, is metabolized by hepatic sulfotransferase into its active form, minoxidil sulfate, after oral administration. This metabolite binds to the sulfonylurea receptor (SUR) component of...
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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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Paracrine Signaling01:21

Paracrine Signaling

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Paracrine signaling allows cells to communicate with their immediate neighbors via secretion of signaling molecules. Such a signal can only trigger a response in nearby target cells because the signal molecules degrade quickly or are inactivated if not taken up. Prominent examples of paracrine signaling include nitric oxide signaling in blood vessels, synaptic signaling of neurons, the blood clotting system, tissue repair/wound healing, and local allergic skin reactions. Nitric oxide as a...
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Measurement of Cyclic Guanosine Monophosphate (cGMP) in Solid Tissues using Competitive Enzyme-Linked Immunosorbent Assay (ELISA)
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The Endothelium-Dependent Nitric Oxide-cGMP Pathway.

F Z Mónica1, K Bian2, F Murad2

  • 1School of Medicine, George Washington University, Washington, DC, United States; State University of Campinas (UNICAMP), Campinas, Brazil.

Advances in Pharmacology (San Diego, Calif.)
|July 25, 2016
PubMed
Summary

The nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway is crucial for cardiovascular health. Targeting this pathway, particularly through soluble guanylyl cyclase (sGC) and phosphodiesterase type 5 (PDE5), offers effective treatments for various circulatory disorders.

Keywords:
Cyclic GMPEndothelial dysfunctionEpigenetic regulationGuanylate cyclaseHeart failureNitric oxideNitric oxide synthasesPhosphodiesterasePulmonary hypertension

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Area of Science:

  • Cardiovascular Physiology
  • Molecular Signaling
  • Pharmacology

Background:

  • Endothelial dysfunction and nitric oxide (NO) deficiency are key contributors to cardiovascular diseases.
  • The NO-cGMP signaling pathway regulates critical physiological functions including smooth muscle tone and platelet activity.

Purpose of the Study:

  • To review the role of endothelial dysfunction in cardiovascular diseases.
  • To explore the therapeutic benefits of regulating cGMP through soluble guanylyl cyclase (sGC) and phosphodiesterase type 5 (PDE5) activation/inhibition.
  • To examine the epigenetic regulation of the NO-sGC pathway in the cardiovascular system.

Main Methods:

  • Review of basic and clinical studies on NO-cGMP signaling.
  • Analysis of therapeutic strategies targeting sGC and PDE5.
  • Investigation of epigenetic mechanisms influencing the NO-sGC pathway.

Main Results:

  • NO-cGMP pathway dysregulation contributes to cardiovascular pathologies.
  • Targeting sGC and PDE5 has yielded successful therapies for pulmonary hypertension, erectile dysfunction, and benign prostatic hyperplasia.
  • Epigenetic factors play a role in regulating NO-sGC pathway components.

Conclusions:

  • The NO-cGMP pathway revolutionized understanding of cardiovascular disease mechanisms.
  • Therapeutic applications targeting NO-cGMP signaling, including sGC stimulators and PDE5 inhibitors, are clinically established.
  • Ongoing research aims to expand therapeutic options for a wider range of diseases targeting this pathway.