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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


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


Insights into the operational model of agonism of receptor dimers

Insights into the operational model of agonism of receptor dimers

Jakubík, J.; Randáková, A. Insights into the Operational Model of Agonism of Receptor Dimers. Expert Opin. Drug Discov. 2022, 17, 1181–1191, doi:10.1080/17460441.2023.2147502. Invited Review. The exact ranking of efficacies and potencies of agonists is indispensable in the discovery of new selective agonists. The operational model of agonism (OMA) is the current standard. Many receptors function as oligomers, requiring an extension of the classical OMA. Extension of OMA by slope factors gives simple equations of functional response that are easy to fit experimental data but results may be inaccurate. Extension of OMA by cooperativity factors gives accurate but complex equations of functional response. Extension of OMA by cooperativity factors should be preferred. More
Nicotinic Acetylcholine Receptors Expressed by Striatal Interneurons Inhibit Striatal Activity and Control Striatal-Dependent Behaviors.

Nicotinic Acetylcholine Receptors Expressed by Striatal Interneurons Inhibit Striatal Activity and Control Striatal-Dependent Behaviors.

Abbondanza, A.; Ribeiro Bas, I.; Modrak, M.; Capek, M.; Minich, J.; Tyshkevich, A.; Naser, S.; Rangotis, R.; Houdek, P.; Sumova, A.; et al. Nicotinic Acetylcholine Receptors Expressed by Striatal Interneurons Inhibit Striatal Activity and Control Striatal-Dependent Behaviors. J. Neurosci. 2022, 42, 2786–2803, doi:10.1523/JNEUROSCI.1627-21.2022. A large variety of nicotinic acetylcholine receptors (nAChRs) are expressed in the striatum, a brain region that is crucial in the control of behaviour. The complexity of receptors with different functions is hindering our understanding of mechanisms through which striatal acetylcholine modulates behaviour. We focused on the role of a small population of beta2-containing nAChRs. We identified neuronal types expressing these receptors and determined their impact on the control of explorative behaviour, anxiety-like behaviour, learning, and sensitivity to stimulants. Additional experiments showed that these alterations were associated with an overall increased activity of striatal neurons. Thus, the small population of nicotinic receptors represents an interesting target for modulation of response to stimulant drugs and other striatal-based behaviour.  More
Neurosteroids and steroid hormones are allosteric modulators of muscarinic receptors

Neurosteroids and steroid hormones are allosteric modulators of muscarinic receptors

Dolejší, E.; Szánti-Pintér, E.; Chetverikov, N.; Nelic, D.; Randáková, A.; Doležal, V.; Kudová, E.; Jakubík, J. Neurosteroids and Steroid Hormones Are Allosteric Modulators of Muscarinic Receptors. Neuropharmacology 2021, 199, 108798, doi:10.1016/j.neuropharm.2021.108798. Some neurosteroids and steroid hormones bind to muscarinic acetylcholine receptors with the affinity of 100 nM or greater Steroids acting at nanomolar concentrations represent the novel pharmacophore of allosteric modulators of muscarinic receptors Corticosterone and progesterone allosterically modulate muscarinic receptors at physiologically relevant concentrations More


Szczurowska; Ewa - Szánti-Pintér; Eszter - Chetverikov; Nikolai - Randáková; Alena - Kudová; Eva - Jakubík; Jan . Modulation of Muscarinic Signalling in the Central Nervous System by Steroid Hormones and Neurosteroids . International Journal of Molecular Sciences. 2023; 24(1)); 507 . IF = 5.6 [ASEP] [ doi ]
Ujčíková; Hana - Roubalová; Lenka - Lee; Y. S. - Slaninová; Jiřina - Brejchová; Jana - Svoboda; Petr . The Dose-Dependent Effects of Multifunctional Enkephalin Analogs on the Protein Composition of Rat Spleen Lymphocytes; Cortex; and Hippocampus; Comparison with Changes Induced by Morphine . Biomedicines. 2022; 10(8)); 1969 . IF = 4.7 [ASEP] [ doi ]
Ujčíková; Hana - Robles; D. - Yue; X. - Svoboda; Petr - Lee; Y. S. - Navratilova; E. Time-Dependent Changes in Protein Composition of Medial Prefrontal Cortex in Rats with Neuropathic Pain . International Journal of Molecular Sciences. 2022; 23(2)); 955 . IF = 5.6 [ASEP] [ doi ]
Ujčíková; Hana - Eckhardt; Adam - Hejnová; L. - Novotný; J. - Svoboda; Petr . Alterations in the Proteome and Phosphoproteome Profiles of Rat Hippocampus after Six Months of Morphine Withdrawal: Comparison with the Forebrain Cortex . Biomedicines. 2022; 10(1)); 80 . IF = 4.7 [ASEP] [ doi ]
Szczurowska; Ewa - Szánti-Pintér; Eszter - Randáková; Alena - Jakubík; Jan - Kudová; Eva . Allosteric Modulation of Muscarinic Receptors by Cholesterol; Neurosteroids and Neuroactive Steroids . International Journal of Molecular Sciences. 2022; 23(21)); 13075 . IF = 5.6 [ASEP] [ doi ]
Jůza; R. - Vojtěchová; I. - Štefková-Mazochová; K. - Dehaen; W. - Petrásek; T. - Prchal; L. - Kobrlová; T. - Janoušek; J. - Vlček; P. - Mezeiová; E. - Svozil; D. - Zdarová Karasová; J. - Pejchal; J. - Stark; H. - Satala; G. - Bojarski; A. J. - Kubacka; M. - Mogilski; S. - Randáková; Alena - Musílek; K. - Soukup; O. - Korábečný; J. Novel D-2/5-HT receptor modulators related to cariprazine with potential implication to schizophrenia treatment . European Journal of Medicinal Chemistry. 2022; 232(Mar 15)); 114193 . IF = 6.7 [ASEP] [ doi ]
Jakubík; Jan - Randáková; Alena . Insights into the operational model of agonism of receptor dimers . Expert Opinion on Drug Discovery. 2022; 17(11); 1181-1191 . IF = 6.3 [ASEP] [ doi ]
Abbondanza; Alice - Bas; Irina Ribeiro - Modrák; Martin - Čapek; Martin - Minich; Jessica - Tyshkevich; Alexandra - Naser; Shahed - Rangotis; Revan - Houdek; Pavel - Sumová; Alena - Dumas; S. - Bernard; V. - Janíčková; Helena . Nicotinic Acetylcholine Receptors Expressed by Striatal Interneurons Inhibit Striatal Activity and Control Striatal-Dependent Behaviors . Journal of Neuroscience. 2022; 42(13); 2786-2803 . IF = 5.3 [ASEP] [ doi ]
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 = 5.288 [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 = 4.297 [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 = 5.780 [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 = 3.195 [ASEP] [ doi ]
Randáková; Alena - Nelic; Dominik - Hochmalová; Martina - Zimčík; Pavel - Mulenga; Mutale Jane - Boulos; J. - Jakubík; Jan . Fusion with Promiscuous G alpha(16) Subunit Reveals Signaling Bias at Muscarinic Receptors . International Journal of Molecular Sciences. 2021; 22(18)); 10089 . IF = 6.208 [ASEP] [ doi ]
Randáková; Alena - Jakubík; Jan . Functionally selective and biased agonists of muscarinic receptors . Pharmacological Research. 2021; 169(July)); 105641 . IF = 10.334 [ASEP] [ doi ]
Kljakic; O. - Al-Onaizi; M. - Janíčková; Helena - Chen; K. S. - Guzman; M. S. - Prado; M. A. M. - Prado; V. F. Cholinergic transmission from the basal forebrain modulates social memory in male mice . European Journal of Neuroscience. 2021; 54(6); 6075-6092 . IF = 3.698 [ASEP] [ doi ]

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

Nikolai Chetverikov, MSc

Postgraduate student

Mgr. Dominik Nelic
Postgraduate student
Trisha Dhabalia

Bc. Mutale Jane Mulenga


Dana Ungerová


Biochemistry of Membrane Receptors

Doc. RNDr. Petr Svoboda, DrSc.
RNDr. Lenka Roubalová, PhD.
RNDr. Hana Ujčíková, PhD.
Junior Scientist