Modulation of GPCRs by monovalent cations and anions

Andrea Strasser; Hans-Joachim Wittmann; Erich H. Schneider; Roland Seifert

doi:10.1007/s00210-014-1073-2

Naunyn-Schmiedeberg's Archives of Pharmacology

March 2015, Volume 388, Issue 3, pp 363–380

Modulation of GPCRs by monovalent cations and anions

Authors
Authors and affiliations

Andrea StrasserEmail author
Hans-Joachim Wittmann
Erich H. Schneider
Roland Seifert

Review

First Online:: 30 November 2014

Received:: 30 October 2014
Accepted:: 17 November 2014

DOI: 10.1007/s00210-014-1073-2

Cite this article as:: Strasser, A., Wittmann, HJ., Schneider, E.H. et al. Naunyn-Schmiedeberg's Arch Pharmacol (2015) 388: 363. doi:10.1007/s00210-014-1073-2

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Abstract

The recent resolution of G-protein-coupled receptor (GPCR) structures in complex with Na⁺ bound to an allosteric modulatory site has renewed interest of the regulation of GPCRs by ions. Here, we summarise key data on ion modulation of GPCRs, obtained in pharmacological, crystallographic, mutagenesis and molecular modelling studies. We show that ion modulation is a highly complex process, involving not only cations but also, rather neglected until now, anions. Pharmacotherapeutic and toxicological aspects are discussed. We provide a mathematical framework for the analysis of ion effects. Finally, we discuss open questions in the field and future research directions. Most importantly, the in vivo relevance of the modulation of GPCR function by monovalent ions must be clarified.

Keywords

GPCR Monovalent cations Monovalent anions Modelling Pharmacology

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Authors and Affiliations

Andrea Strasser
- 1
Email author
Hans-Joachim Wittmann
- 2
Erich H. Schneider
- 3
Roland Seifert
- 3

1.Department of Pharmaceutical/Medicinal Chemistry IIUniversity of RegensburgRegensburgGermany
2.Faculty of Chemistry/PharmacyUniversity of RegensburgRegensburgGermany
3.Institute of PharmacologyMedical School of HannoverHannoverGermany

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Modulation of GPCRs by monovalent cations and anions

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