Journal article

Publication year: 2016

Journal: Scientific Reports

Volume number: 6

ISSN: 2045-2322

Open access status: Gold

DOI Link: https://doi.org/10.1038/srep28660

Publisher: Nature Research

Abstract: 
We demonstrated previously that phosphocholine and phosphocholine-modified macromolecules efficiently inhibit ATP-dependent release of interleukin-1 beta from human and murine monocytes by a mechanism involving nicotinic acetylcholine receptors (nAChR). Interleukin-1 beta is a potent pro-inflammatory cytokine of innate immunity that plays pivotal roles in host defence. Control of interleukin-1 beta release is vital as excessively high systemic levels cause life threatening inflammatory diseases. In spite of its structural similarity to acetylcholine, there are no other reports on interactions of phosphocholine with nAChR. In this study, we demonstrate that phosphocholine inhibits ion-channel function of ATP receptor P2X7 in monocytic cells via nAChR containing alpha 9 and alpha 10 subunits. In stark contrast to choline, phosphocholine does not evoke ion current responses in Xenopus laevis oocytes, which heterologously express functional homomeric nAChR composed of alpha 9 subunits or heteromeric receptors containing alpha 9 and alpha 10 subunits. Preincubation of these oocytes with phosphocholine, however, attenuated choline-induced ion current changes, suggesting that phosphocholine may act as a silent agonist. We conclude that phophocholine activates immuno-modulatory nAChR expressed by monocytes but does not stimulate canonical ionotropic receptor functions.

Harvard Citation style: Richter, K., Mathes, V., Fronius, M., Althaus, M., Hecker, A., Krasteva-Christ, G., et al. (2016) Phosphocholine - an agonist of metabotropic but not of ionotropic functions of α9-containing nicotinic acetylcholine receptors, Scientific Reports, 6, Article 28660. https://doi.org/10.1038/srep28660

APA Citation style: Richter, K., Mathes, V., Fronius, M., Althaus, M., Hecker, A., Krasteva-Christ, G., Padberg, W., Hone, A., McIntosh, J., Zakrzewicz, A., & Grau, V. (2016). Phosphocholine - an agonist of metabotropic but not of ionotropic functions of α9-containing nicotinic acetylcholine receptors. Scientific Reports. 6, Article 28660. https://doi.org/10.1038/srep28660