ANG II AT1 and AT2 receptors both inhibit bFGF-induced proliferation of bovine adrenocortical cells

P Liakos1, N Bourmeyster, G Defaye

  • 1Institut National de la Santé et de la Recherche Médicale, Unité 244, Centre d'Etudes Nucléaires de Grenoble, France.

Insights

Angiotensin II (ANG II) inhibits cell growth by affecting both AT1 and AT2 receptors in bovine adrenal cells. This study reveals distinct pathways for ANG II

Area of Science:

  • Endocrinology
  • Cell Biology
  • Molecular Biology

Background:

  • Angiotensin II (ANG II) exerts pressor and growth effects via the AT1 receptor.
  • The AT2 receptor's antiproliferative mechanisms are not fully understood.
  • ANG II's role in cell proliferation requires further elucidation.

Purpose of the Study:

  • To investigate the effects of ANG II on cell proliferation in bovine adrenal fasciculata cells.
  • To delineate the roles of AT1 and AT2 receptors in ANG II-mediated growth inhibition.
  • To identify the signaling pathways involved in ANG II's antimitogenic actions.

Main Methods:

  • Treatment of bovine adrenal fasciculata cells with ANG II, bFGF, and receptor-specific agonists/antagonists.
  • Assessment of DNA synthesis and cell cycle progression (G1 phase).
  • Analysis of cyclin D1 expression and kinase activity, and evaluation of signaling pathway involvement (COX, tyrosine phosphatase, pertussis toxin).

Main Results:

  • ANG II inhibited basic fibroblast growth factor (bFGF)-induced DNA synthesis and arrested cells in G1 phase.
  • ANG II reduced cyclin D1 expression and associated kinase activity.
  • Both AT1 and AT2 receptors contributed to the antimitogenic effect, with distinct signaling pathways: AT1 via prostaglandin synthesis and AT2 via tyrosine phosphatase activation.

Conclusions:

  • ANG II inhibits bFGF-induced proliferation in bovine adrenal fasciculata cells through both AT1 and AT2 receptors.
  • The AT1 receptor mediates its effect by stimulating prostaglandin synthesis.
  • The AT2 receptor utilizes a pathway involving protein tyrosine phosphatase activation.

Related Concept Videos

Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

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 cells.
Two...
Adrenergic Receptors: β Subtype01:26

Adrenergic Receptors: β Subtype

β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors have equal affinities for...
Antihypertensive Drugs: Action of β1 Blockers01:17

Antihypertensive Drugs: Action of β1 Blockers

β1-receptors are primarily located in the heart and kidneys. In cardiac myocytes, these receptors interact with neurotransmitters released by the sympathetic nervous system during heightened activity or danger. As a result, β1-receptors get activated, initiating a series of biochemical processes. Excessive activation of beta receptors due to chronic stress can abnormally increase heart rate and contractility, resulting in high blood pressure or hypertension. To counteract this, β1-blockers...
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...