Related Experiment Videos
The angiotensin II AT2 receptor inhibits proliferation and promotes differentiation in PC12W cells
S Meffert1, M Stoll, U M Steckelings
1Department of Pharmacology, Christian-Albrechts-University, Kiel, Germany.
Abstract:
Angiotensin II (ANG II) has been implicated in cell growth and differentiation. We investigated the effect of AT2 receptor stimulation on proliferation and morphological differentiation in cells of neuronal origin by using the pheochromocytoma derived cell line, PC12W. ANG II (10(-8)-10(-6) M) inhibited fetal calf serum (FCS)-induced cell proliferation in a concentration dependent manner. In half of the experiments, the epidermal growth factor (EGF) exerted a mitogenic action which was concentration-dependently inhibited by ANG II. In the other half of the experiments, EGF had an antimitogenic effect which was further enhanced by ANG II (maximally at 10(-6) M). Treatment with nerve growth factor (NGF) induced an inhibition of [3H]thymidine incorporation, which was enhanced by ANG II, maximally 25% at the highest concentration. The effects of ANG II on [3H]thymidine incorporation were reflected by those on cell number and were prevented by the AT2 receptor antagonist, PD123177, but not influenced by the AT1 receptor antagonist, losartan. The ANG II-induced inhibition of cell proliferation was paralleled by morphological differentiation in response to daily treatment with ANG II. ANG II also enhanced low-dose NGF-induced neurite formation. Again, these effects of ANG II were abolished by the AT2 receptor antagonist, PD123177. Our data in PC12W cells show that the AT2 receptor not only inhibits growth factor-induced proliferation and enhances the NGF-mediated growth arrest but also induces morphological differentiation in cells of neuronal origin. These findings strongly support the hypothesis that the AT2 receptor promotes differentiation in neuronal cells.
Insights
Stimulating the AT2 receptor with Angiotensin II (ANG II) inhibits neuronal cell proliferation and promotes differentiation. This effect is mediated via the AT2 receptor, not the AT1 receptor, suggesting a key role in neuronal development.
Area of Science:
- Neuroscience
- Cell Biology
- Endocrinology
Background:
- Angiotensin II (ANG II) is known to influence cell growth and differentiation.
- The specific role of the AT2 receptor in neuronal cell development requires further elucidation.
Purpose of the Study:
- To investigate the effect of AT2 receptor stimulation on the proliferation and morphological differentiation of neuronal cells.
- To determine the involvement of AT2 receptors in mediating these cellular responses.
Main Methods:
- Utilized the PC12W pheochromocytoma cell line for experiments.
- Administered Angiotensin II (ANG II) at varying concentrations (10(-8)-10(-6) M).
- Employed AT2 receptor antagonist PD123177 and AT1 receptor antagonist losartan to assess receptor specificity.
Main Results:
- ANG II inhibited fetal calf serum (FCS)-induced proliferation in a dose-dependent manner.
- ANG II modulated epidermal growth factor (EGF) effects on proliferation, either inhibiting or enhancing them.
- ANG II enhanced nerve growth factor (NGF)-induced growth arrest and neurite formation, effects blocked by PD123177.
Conclusions:
- AT2 receptor stimulation inhibits growth factor-induced proliferation in neuronal cells.
- AT2 receptor activation enhances NGF-mediated growth arrest and promotes morphological differentiation.
- These findings support the hypothesis that the AT2 receptor plays a crucial role in promoting neuronal cell differentiation.