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Phosphocholine – an agonist of metabotropic but not of ionotropic functions of α9-containing nicotinic acetylcholine receptors

Lookup NU author(s): Dr Mike Althaus

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Abstract

We demonstrated previously that phosphocholine and phosphocholine-modified macromolecules efficiently inhibit ATP-dependent release of interleukin-1β from human and murine monocytes by a mechanism involving nicotinic acetylcholine receptors (nAChR). Interleukin-1β is a potent pro-inflammatory cytokine of innate immunity that plays pivotal roles in host defence. Control of interleukin-1β 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 α9 and α10 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 α9 subunits or heteromeric receptors containing α9 and α10 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.

Publication metadata

Author(s): Richter K, Mathes V, Fronius M, Althaus M, Hecker G, Krasteva-Christ G, Padberg W, Hone AJ, McIntosh JM, Zakrzewicz A, Grau V

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2016

Volume: 6

Issue: 6

Print publication date: 28/06/2016

Online publication date: 28/06/2016

Acceptance date: 06/06/2016

Date deposited: 22/11/2018

ISSN (electronic): 2045-2322

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/srep28660

DOI: 10.1038/srep28660

PubMed id: 27349288

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