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Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors01:30

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Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
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The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
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In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
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The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
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Indirect-acting adrenergic agonists potentiate the effects of endogenous catecholamines through different mechanisms without directly binding to adrenoceptors.
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The liver plays a pivotal role in eliminating drugs and their metabolites, primarily through a process known as biliary excretion. This process involves the hepatocytes, the primary cells in the liver that generate bile. A range of transporters actively expels polar drugs or hydrophilic drug metabolites into the bile, which transports the drugs and metabolites into the small intestine. From here, they are eventually expelled from the body through feces. In some instances, the original drug or a...
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Production of Pseudotyped Particles to Study Highly Pathogenic Coronaviruses in a Biosafety Level 2 Setting
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Bypassing ACE2.

John F Foley1

  • 1Science Signaling, AAAS, Washington, DC 20005, USA.

Science Signaling
|August 15, 2023
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Summary
This summary is machine-generated.

The SARS-CoV-2 virus can enter cells using a lysosomal protein, bypassing the need for ACE2. This discovery offers new insights into viral entry mechanisms and potential therapeutic targets.

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Area of Science:

  • Virology
  • Cell Biology
  • Molecular Medicine

Background:

  • The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to utilize the angiotensin-converting enzyme 2 (ACE2) receptor for cellular entry.
  • Understanding alternative viral entry pathways is crucial for developing effective antiviral strategies.

Purpose of the Study:

  • To investigate whether SARS-CoV-2 can infect cells through mechanisms independent of ACE2.
  • To identify novel cellular receptors involved in SARS-CoV-2 cell entry.

Main Methods:

  • Cell-based assays were performed to assess viral entry.
  • Experiments utilized cell lines with varying ACE2 expression levels.
  • Immunofluorescence and biochemical methods were employed to identify viral binding partners.

Main Results:

  • SARS-CoV-2 successfully entered cells lacking ACE2 expression.
  • A specific lysosomal transmembrane protein was identified as a binding partner for the SARS-CoV-2 spike protein.
  • This interaction facilitated viral entry into cells.

Conclusions:

  • Cellular entry of SARS-CoV-2 is not solely dependent on ACE2.
  • Lysosomal transmembrane proteins represent an alternative pathway for SARS-CoV-2 cell entry.
  • Targeting this novel pathway could offer new therapeutic avenues against SARS-CoV-2 infection.