Related Experiment Video

Updated: Jun 26, 2026

Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors
12:03

Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors

Published on: June 7, 2016

Coupling factor 6 enhances Src-mediated responsiveness to angiotensin II in resistance arterioles and cells

Tomohiro Osanai1, Hirofumi Tomita, Motoi Kushibiki

  • 1Department of Cardiology, Hirosaki University Graduate School of Medicine, 5 Zaifu-Cho, Hirosaki 036-8562, Japan. osanait@cc.hirosaki-u.ac.jp

Cardiovascular Research
|December 25, 2008
PubMed

Insights

Coupling factor 6 (CF6) directly enhances calcium (Ca2+) signaling in vascular smooth muscle cells (VSMCs), leading to vasoconstriction and hypertension. This occurs via c-Src activation, mediated by CF6 binding to the F1 motor of ATP synthase.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Biology
  • Hypertension Research

Background:

  • Coupling factor 6 (CF6) is known to induce hypertension by reducing prostacyclin production.
  • The precise intracellular signaling mechanisms of CF6 in vascular smooth muscle cells (VSMCs) related to vasoconstriction remain unclear.

Purpose of the Study:

  • To investigate the direct effects of CF6 on calcium (Ca2+) signaling in cultured VSMCs.
  • To elucidate the in vivo role of endogenous CF6 in hypertension development using CF6 transgenic (TG) mice.

Main Methods:

  • Assessed Ca2+ signaling in VSMCs and vasoconstriction in mesenteric arterioles from CF6-TG mice and spontaneously hypertensive rats (SHRs).
  • Utilized nifedipine-sensitive Ca2+ channels, anti-CF6 antibodies, and a c-Src inhibitor (PP1).
  • Identified the CF6 receptor as the F1 motor of ATP synthase.

Main Results:

  • Exogenous CF6 increased intracellular Ca2+ ([Ca2+]i) in VSMCs via nifedipine-sensitive channels.
  • CF6 potentiated angiotensin II-induced vasoconstriction and [Ca2+]i spikes in VSMCs from SHRs and in mesenteric arterioles from CF6-TG mice.
  • Inhibition of c-Src blocked CF6-induced Ca2+ signaling and vasoconstriction.
  • CF6 decreased intracellular pH and activated c-Src, particularly in SHR-derived VSMCs, due to increased ATPase activity.

Conclusions:

  • CF6 directly enhances Ca2+ signaling in VSMCs, contributing to hypertension.
  • CF6-induced vasoconstriction in mesenteric arterioles is mediated by c-Src activation.
  • The F1 motor of ATP synthase serves as a receptor for CF6, with higher affinity in SHRs.
Abstract

More Related Videos

Evaluation of Vascular Control Mechanisms Utilizing Video Microscopy of Isolated Resistance Arteries of Rats10:28

Evaluation of Vascular Control Mechanisms Utilizing Video Microscopy of Isolated Resistance Arteries of Rats

Published on: December 5, 2017

Related Concept Videos

Antihypertensive Drugs: Angiotensin II Receptor Blockers01:30

Antihypertensive Drugs: Angiotensin II Receptor Blockers

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...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors01:30

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors

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...
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

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...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Antihypertensive Drugs: Direct Renin Inhibitors01:25

Antihypertensive Drugs: Direct Renin Inhibitors

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,...