Influence of St. John’s wort extract Ze 117 on the lateral mobility of β₁-adrenergic receptors in C6 cells

Introduction Since St. John’s wort affects the signal transduction of serotonergic, dopaminergic and adrenergic neurotransmitter systems, Ze 117 is used for the treatment of depressive episodes. Signaling relies not only on receptor-ligand interactions and subsequent regulatory processes, but also on lateral receptor mobility [1].

Aim Aim of the study was to investigate the influence of Ze 117 on the lateral mobility of β₁-adrenergic receptors (β₁AR) in C6 cells.

Method Influence of Ze 117 on lateral mobility of SNAP-tagged β₁AR in the plasma membrane of C6 cells was investigated under both, non-stimulating and isoprenaline-stimulating conditions. Single particle tracking (SPT) was used, whereby the registered trajectories were evaluated by variational Bayesian treatment of a hidden Markov model (vbSPT) and packing coefficient (Pc) analysis with respect to diffusion coefficients, receptor state occupancies and confinement.

Results Under non-stimulating conditions decreased receptor mobility and increased confinement were found for Ze 117 pre-treated C6 cells compared to control. After stimulation of control cells, the slow receptor diffusion was more pronounced, whereas confinement was not affected. In contrast, stimulation of Ze 117 pre-treated C6 cells showed increased confinement but no additional effect on the behaviour of slow diffusing receptors.

Conclusion SPT is a powerful method to analyze lateral receptor mobility, which is related to biological and pharmacological effects. Lateral receptor mobility is influenced by Ze 117 and represents a possible therapeutically relevant contribution to the mode of action.

Acknowledgements We thank Zeller AG for financial support.

Publication History

Article published online:
13 June 2022

• References

• 1 Snaar-Jagalsk B. Methods Enzymol 2013; 521: 47-67