Intranet Campus web

INSTITUTE OF PHYSIOLOGY CAS

Cutting-edge science for health

Laboratory of Neurochemistry

Laboratory of Neurochemistry

1. Neurochemistry Group

We study physiology, biochemistry and pharmacology of cholinergic neurons at the molecular level and molecular pharmacology of other GPCRs. In our study, we mainly employ cell lines but we also use animal models. Our research is focused mainly on these topics:

  • biochemical physiology and pharmacology of cholinergic neurons
  • development and differentiation of cholinergic neurons
  • synthesis, storage, and release of acetylcholine
  • presynaptic regulation of acetylcholine release
  • cholinergic mechanisms in the pathogenesis of Alzheimer´s disease
  • influence of beta-amyloid on acetylcholine metabolism and muscarinic transmission
  • molecular pharmacology of muscarinic receptors
  • allosteric modulation of receptor activation.
  • interaction of receptors with G-proteins
  • modelling of muscarinic receptor signal transduction.

2. Group of Biochemistry of Membrane Receptors

The research focuses on the cellular and molecular mechanisms of desensitization of hormone response mediated by the activation of G protein-coupled receptors (GPCR). G protein-coupled receptors are plasma membrane integral proteins that serve as transducers of extracellular signals across the plasma membrane bilayer to the cell interior. GPCR play a key role in the regulation of many physiological processes and functions. Moreover, GPCRs represent one of the most important groups of targets for therapeutics. The main areas of the research are:

  • role of the cell membrane and membrane domains
  • opioid receptors and drug addiction
  • effect of monovalent ions on δ-opioid receptors – analysis of lithium effect in living cells and isolated cell membranes.

Publication 2015 - 2021

Projects

Cholinergic modulation of striatum-based behaviour

The aim of the project is to determine how disruption of cholinergic activation of striatal GABAergic interneurons alters striatal signalling and striatum-based behaviour by using a mouse model with deletion of the β2 nicotinic acetylcholine receptor subunit in striatal GABAergic interneurons. More

Opioid receptors and drug addiction

Addiction to opioid drugs (opioids) represents one of the most severe forms of drug abuse. Opium is one of the oldest known drugs and is used for its medicinal and euphoric effects for thousands of years. Opioid dependence develops as a consequence of changes in the central nervous system (CNS) induced by prolonged exposure to opioid drugs, e.g., morphine, codein or heroin.   More

The effect of monovalent ions on delta-opioid receptors – analysis of lithium effect in living cells and isolated cell membranes

Activity of opioid receptor (OR) is among others modulates by monovalent cations especially by sodium (Na+) and lithium (Li+) which atomic radius is very similar to those of sodium. Lithium is used in psychiatry as a mood stabilizer (see review article Vošahlíková and Svoboda, 2016). Monovalent ions modulate GPCR signalling in not fully understood mechanism. More

The role of cell membrane and membrane domains

Cell (plasma) membrane (PM) serves as a protective barrier, but also plays a role in the cellular communication. The integrity of hydrophobic lipid environment of PM is an important factor affecting function of membrane proteins. More

Achievements

Agonist-specific conformations of the M<sub>2</sub> muscarinic acetylcholine receptor assessed by molecular dynamics

Structurally diverse agonists for a given receptor induce receptor conformations specific to each structural family. These agonist-specific conformations can lead to non-uniform modulation of signalling pathways. This preferential orientation of signalling of a given receptor towards a subset of its signal transducers is termed signalling bias. This property may be employed to develop drugs that selectively produce desired effects while avoiding side effects associated with activation of unwanted signalling pathways. We modelled conformations of the M2 receptor specific to individual agonists, including the newly developed Gi-biased agonists. More

Role of membrane cholesterol in differential sensitivity of muscarinic receptor subtypes to persistently bound xanomeline

Our new publication in journal Neuropharmacology in which we demonstrate that membrane cholesterol plays an important and subtype-specific role in activation of muscarinic acetylcholine receptors. To our knowledge, this is the first demonstration of pharmacological selectivity due to differences in receptor-membrane interactions at any GPCR. The possibility to achieve pharmacological selectivity based on receptor-membrane interactions changes our view on the molecular basis of pharmacological selectivity and opens new ways for the development of a novel pharmaceutics. More

Book: Muscarinic Receptor: From Structure to Animal Models

Dr. Jan Jakubik Institute of Physiology Academy of Sciences and professor. Jaromir Mysliveček Institute of Physiology 1st Faculty of Medicine were approached to write the current list of methods that are used in research of muscarinic receptor as part of a Neuromethods series published by Springer. More

Publications

Vošahlíková; Miroslava - Roubalová; Lenka - Brejchová; Jana - Alda; M. - Svoboda; Petr . Therapeutic lithium alters polar head-group region of lipid bilayer and prevents lipid peroxidation in forebrain cortex of sleep-deprived rats . Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids. 2021; 1866(9)); 158962 . IF = 4.698 [ASEP] [ doi ]
Ujčíková; Hana - Hejnová; L. - Eckhardt; Adam - Roubalová; Lenka - Novotný; J. - Svoboda; Petr . Impact of three-month morphine withdrawal on rat brain cortex; hippocampus; striatum and cerebellum: proteomic and phosphoproteomic studies . Neurochemistry International. 2021; 144(Mar)); 104975 . IF = 3.921 [ASEP] [ doi ]
Staszewski; M. - Nelic; Dominik - Jończyk; J. - Dubiel; M. - Frank; A. - Stark; H. - Bajda; M. - Jakubík; Jan - Walczyński; K. Guanidine Derivatives: How Simple Structural Modification of Histamine H3R Antagonists Has Led to the Discovery of Potent Muscarinic M2R/M4R Antagonists . ACS Chemical Neuroscience. 2021; 12(13); 2503-2519 . IF = 4.418 [ASEP] [ doi ]
Roubalová; Lenka - Vošahlíková; Miroslava - Slaninová; Jiřina - Kaufman; Jonáš - Alda; M. - Svoboda; Petr . Tissue-specific protective properties of lithium: comparison of rat kidney; erythrocytes and brain . Naunyn-Schmiedeberg's Archives of Pharmacology. 2021; 394(5); 955-965 . IF = 3.000 [ASEP] [ doi ]
Randáková; Alena - Jakubík; Jan . Functionally selective and biased agonists of muscarinic receptors . Pharmacological Research. 2021; 169(July)); 105641 . IF = 7.658 [ASEP] [ doi ]

Article photogallery

The entire photogallery

People

Mgr. Jan Jakubík, PhD
Head of the Laboratory
MUDr. Vladimír Doležal, DrSc.
Deputy Head of the Laboratory
MUDr. et Mgr. Helena Janíčková, PhD
Scientist
Mgr. Eva Dolejší, PhD
Junior Scientist
Mgr. Alena Randáková, PhD
Junior Scientist
Alice Abbondanza, MSc
Postgraduate Student

Nikolai Chetverikov, MSc

Postgraduate student

Denise Greco, MSc

Research Assistant

Bc. Jana Bláhová
Student
Trisha Dhabalia
Student

Bc. Mutale Jane Mulenga

Student

Bc. Dominik Nelic
Student
Bc. Alexandra Tyshkevich
Student
Dana Ungerová
Technician
 

Bc. Jan Eliáš

External Research Assistant

 

 

Biochemistry of Membrane Receptors

Doc. RNDr. Petr Svoboda, DrSc.
Scientist
RNDr. Lenka Roubalová, PhD.
Scientist
RNDr. Hana Ujčíková, PhD.
Junior Scientist
Ing. Miroslava Vošahlíková, PhD.
Junior Scientist
Mgr. Jana Brejchová, PhD.
Junior Scientist
 

Mgr. Ivana Švandová
Research Assistant

  Bc. Jonáš Kaufman
Student