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Updated: Aug 9, 2026

Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors
Published on: June 7, 2016
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.
Abstract:
Angiotensin II (ANG II) has long been known for its pressor and growth-promoting effects, which are both mediated by the AT1 receptor. By contrast, the AT2 receptor has recently been reported to mediate inhibition of proliferation through as yet undefined mechanisms. We report here that in bovine adrenal fasciculata cells ANG II by itself does not affect growth but inhibits basic fibroblast growth factor (bFGF)-induced DNA synthesis and blocks the cells in G1 phase. Consistent with this, ANG II inhibits cyclin D1 expression and cyclin D1-associated kinase activity. The antimitogenic effect of ANG II is partly mimicked by the AT2-selective agonist CGP-42112. It is also blocked partly and in an additive fashion by the AT1- and AT2-selective antagonists losartan and PD-123319, indicating the contribution of both receptor subtypes to this response. AT1-dependent antiproliferation is selectively blocked by the cyclooxygenase inhibitor indomethacin and restored by prostaglandin E2, whereas AT2-receptor-mediated inhibition of growth is suppressed by the tyrosine phosphatase inhibitors orthovanadate and bpV(pic). Both pathways are, however, pertussis toxin sensitive. We hypothesize that, in fasciculata cells, the AT1 receptor inhibits bFGF-induced proliferation by stimulating prostaglandin synthesis, whereas the AT2 receptor mediates its effect through a pathway that requires protein tyrosine phosphatase activation.
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.
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