Antidepressants are modifiers of lipid bilayer properties

The Journal of General Physiology
Ruchi KapoorOlaf S Andersen

Abstract

The two major classes of antidepressants, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), inhibit neurotransmitter reuptake at synapses. They also have off-target effects on proteins other than neurotransmitter transporters, which may contribute to both desired changes in brain function and the development of side effects. Many proteins modulated by antidepressants are bilayer spanning and coupled to the bilayer through hydrophobic interactions such that the conformational changes underlying their function will perturb the surrounding lipid bilayer, with an energetic cost (ΔGdef) that varies with changes in bilayer properties. Here, we test whether changes in ΔGdef caused by amphiphilic antidepressants partitioning into the bilayer are sufficient to alter membrane protein function. Using gramicidin A (gA) channels to probe whether TCAs and SSRIs alter the bilayer contribution to the free energy difference for the gramicidin monomer⇔dimer equilibrium (representing a well-defined conformational transition), we find that antidepressants alter gA channel activity with varying potency and no stereospecificity but with different effects on bilayer elasticity and intrinsic curvature. Measuring the...Continue Reading

References

Dec 20, 1979·Biochimica Et Biophysica Acta·P R Cullis, B de Kruijff
Oct 17, 1977·Biochimica Et Biophysica Acta·J N IsraelachviliB W Ninham
Jun 1, 1976·The Journal of General Physiology·O S AndersenA Cass
May 15, 1983·Journal of Molecular Biology·B A Lewis, D M Engelman
Jan 1, 1993·The Journal of Neuropsychiatry and Clinical Neurosciences·C N KarsonR A Komoroski
Oct 1, 1996·Nature Structural Biology·W C Wimley, S H White
Jul 1, 1996·Pharmacology & Toxicology·T Narahashi
Nov 25, 1997·Biophysical Journal·M R Wenk, J Seelig
Apr 17, 1998·Biophysical Journal·C NielsenO S Andersen
Jan 23, 1999·Methods in Enzymology·D V GreathouseO S Andersen
Jun 24, 1999·Cellular and Molecular Neurobiology·C L DeVane
Sep 16, 2000·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·N R BoloJ P Macher
Oct 29, 2000·Biophysical Journal·C Nielsen, O S Andersen
Nov 25, 2000·Biochimica Et Biophysica Acta·H Heerklotz, J Seelig
Mar 20, 2002·Current Topics in Medicinal Chemistry·A Avdeef
Aug 31, 2002·Biophysical Journal·Anmin TanJoachim Seelig
Nov 1, 1958·The American Journal of Psychiatry·R KUHN
Feb 1, 1961·The American Journal of Psychiatry·J A BARSA, J C SAUDERS
Apr 3, 2004·Nature Reviews. Drug Discovery·Bryan L RothWesley K Kroeze
Jun 22, 2005·Molecular Pharmacology·J A LundbaekO S Andersen
Jan 31, 2006·Current Opinion in Structural Biology·Andrew L HopkinsJohn P Overington
May 2, 2007·British Journal of Pharmacology·P K Gillman
May 29, 2007·Molecular Pharmaceutics·Sanjivanjit K BhalGreg M Pearl
May 31, 2007·Proceedings of the National Academy of Sciences of the United States of America·Michael J BrunoOlaf S Andersen
Aug 21, 2007·Biochemistry·Helgi I IngolfssonOlaf S Andersen
Oct 6, 2007·Molecular Neurobiology·Gerhard Rammes, Rainer Rupprecht
Jan 4, 2008·The New England Journal of Medicine·R H Belmaker, Galila Agam
Aug 21, 2008·Anesthesia and Analgesia·Edmond I EgerJames M Sonner
Dec 11, 2008·Journal of Visualized Experiments : JoVE·Helgi IngolfsonOlaf Sparre Andersen
Dec 17, 2008·Journal of Visualized Experiments : JoVE·Ruchi KapoorOlaf Sparre Andersen
Nov 21, 2009·Analytical Biochemistry·Maria João MorenoAdrian Velazquez-Campoy
Nov 27, 2009·Journal of the Royal Society, Interface·Jens A LundbaekOlaf S Andersen
Feb 6, 2010·British Journal of Pharmacology·A Tanti, C Belzung

❮ Previous
Next ❯

Citations

Jan 28, 2021·Chemistry : a European Journal·Simli DeySudipta Maiti
Apr 10, 2021·The Journal of General Physiology·Mohammad-Reza GhovanlooPeter C Ruben
Apr 8, 2021·ACS Chemical Neuroscience·Xingyuan ZouMaikel C Rheinstädter
May 25, 2021·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Mohammad-Reza Ghovanloo, Peter C Ruben
Jan 1, 2022·Molecular Psychiatry·Steven D TargumMark M Rasenick

❮ Previous
Next ❯

Methods Mentioned

BETA
isothermal titration calorimetry
size-exclusion chromatography
fluorescence assay

Software Mentioned

OriginLab
Matlab
Percepta
Percepta PhysChem Suite
Origin
ACD

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.