Reet Reinart-Okugbeni "Katsesüsteemid ligandide sidumisomaduste ja aktiivsuse alatüüp-selektiivseks iseloomustamiseks dopamiini retseptoritel" | University of Tartu

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Faculty of Arts and Humanities
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+372 737 5341
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Jakobi 2, rooms 116–121, 51005 Tartu
  • Dean's Office
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    Faculty address: 
    Jakobi 2, rooms 116–121, 51005 Tartu
  • Institute of History and Archaeology
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    Faculty address: 
    Jakobi 2, 51005 Tartu
  • Institute of Estonian and General Linguistics
    Faculty phone: 
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    Faculty address: 
    Jakobi 2, 51005 Tartu
  • Institute of Philosophy and Semiotics
    Faculty phone: 
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    Faculty address: 
    Jakobi 2, rooms 309–352, 51005 Tartu
  • Institute of Cultural Research
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    Faculty address: 
    Ülikooli 16, 51003 Tartu
  • School of Theology and Religious Studies
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    +372 737 5301
    Faculty address: 
    Ülikooli 18–310, 50090 Tartu
  • College of Foreign Languages and Cultures
    Faculty address: 
    J. Liivi 4, 50409, Tartu
  • Viljandi Culture Academy
    Faculty phone: 
    +372 435 5232
    Faculty address: 
    Posti 1, 71004 Viljandi
Faculty of Social Sciences
Faculty phone: 
+372 737 5957
Faculty address: 
Lossi 36, 51003 Tartu
  • Dean's Office
    Faculty phone: 
    + 372 737 5900
    Faculty address: 
    Lossi 36, 51003 Tartu
  • Institute of Education
    Faculty phone: 
    +372 737 6440
    Faculty address: 
    Salme 1a–29, 50103 Tartu
  • Johan Skytte Institute of Political Studies
    Faculty phone: 
    +372 737 5582
    Faculty address: 
    Lossi 36–301, 51003 Tartu
  • School of Economics and Business Administration
    Faculty phone: 
    +372 737 6310
    Faculty address: 
    Narva mnt 18, 51009 Tartu
  • Institute of Psychology
    Faculty phone: 
    +372 737 5902
    Faculty address: 
    Näituse 2, 50409 Tartu
  • School of Law
    Faculty phone: 
    +372 737 5390
    Faculty address: 
    Näituse 20–324, 50409 Tartu
  • Institute of Social Studies
    Faculty phone: 
    +372 737 5188
    Faculty address: 
    Lossi 36, 51003 Tartu
  • Narva College
    Faculty phone: 
    +372 740 1900
    Faculty address: 
    Raekoja plats 2, 20307 Narva
  • Pärnu College
    Faculty phone: 
    +372 445 0520
    Faculty address: 
    Ringi 35, 80012 Pärnu
Faculty of Medicine
Faculty phone: 
+372 737 5326
Faculty address: 
Ravila 19, 50411 Tartu
  • Dean's Office
    Faculty phone: 
    +372 737 5326
    Faculty address: 
    Ravila 19, 50411 Tartu
  • Institute of Biomedicine and Translational Medicine
    Faculty phone: 
    +372 737 4210
    Faculty address: 
    Biomeedikum, Ravila 19, 50411 Tartu
  • Institute of Pharmacy
    Faculty phone: 
    +372 737 5286
    Faculty address: 
    Nooruse 1, 50411 Tartu
  • Institute of Dentistry
    Faculty phone: 
    +372 731 9856
    Faculty address: 
    Raekoja plats 6, 51003 Tartu
  • Institute of Clinical Medicine
    Faculty phone: 
    +372 737 5323
    Faculty address: 
    L. Puusepa 8, 50406 Tartu
  • Institute of Family Medicine and Public Health
    Faculty phone: 
    +372 737 4190
    Faculty address: 
    Ravila 19, 50411 Tartu
  • Institute of Sport Sciences and Physiotherapy
    Faculty phone: 
    +372 737 5360
    Faculty address: 
    Jakobi 5–205, 51005 Tartu
Faculty of Science and Technology
Faculty phone: 
+372 737 5820
Faculty address: 
Vanemuise 46–208, 51014 Tartu
  • Dean's Office
    Faculty phone: 
    +372 737 5820
    Faculty address: 
    Vanemuise 46–208, 51003 Tartu
  • Institute of Computer Science
    Faculty phone: 
    +372 737 5445
    Faculty address: 
    Narva mnt 18, 51009 Tartu
  • Estonian Marine Institute
    Faculty phone: 
    +372 671 8902
    Faculty address: 
    Mäealuse 14, 12618 Tallinn
  • Institute of Physics
    Faculty address: 
    W. Ostwaldi 1, 50411 Tartu
  • Institute of Chemistry
    Faculty phone: 
    +372 737 5261
    Faculty address: 
    Ravila 14a, 50411 Tartu
  • Institute of Mathematics and Statistics
    Faculty phone: 
    +372 737 5860
    Faculty address: 
    Narva mnt 18, 51009 Tartu
  • Institute of Molecular and Cell Biology
    Faculty phone: 
    +372 737 5027
    Faculty address: 
    Riia 23, 23b–134, 51010 Tartu
  • Tartu Observatory
    Faculty phone: 
    +372 737 4510
    Faculty address: 
    Observatooriumi 1, Tõravere, 61602 Tartumaa
  • Institute of Technology
    Faculty phone: 
    +372 737 4800
    Faculty address: 
    Nooruse 1, 50411 Tartu
  • Institute of Ecology and Earth Sciences
    Faculty phone: 
    +372 737 5835
    Faculty address: 
    Vanemuise 46, 51003 Tartu
Institutions
  • Library
    Faculty phone: 
    +372 737 5702
    Faculty address: 
    W. Struve 1, 50091 Tartu
  • Youth Academy
    Faculty phone: 
    +372 737 5581
    Faculty address: 
    Uppsala 10, 51003 Tartu
  • Institute of Genomics
    Faculty phone: 
    +372 737 4000
    Faculty address: 
    Riia 23b, 51010 Tartu
  • Museum
    Faculty phone: 
    +372 737 5674
    Faculty address: 
    Lossi 25, 51003 Tartu
  • University of Tartu Natural History Museum and Botanical Garden
    Faculty phone: 
    +372 737 6076
    Faculty address: 
    Vanemuise 46, 51003 Tartu
Support Units
  • Administrative Office
    Faculty phone: 
    +372 737 5606
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Centre for Entrepreneurship and Innovation
    Faculty phone: 
    +372 737 4809
    Faculty address: 
    Narva mnt 18, 51009, Tartu
  • University Office in Tallinn
    Faculty phone: 
    +372 737 6600
    Faculty address: 
    Teatri väljak 3, 10143 Tallinn
  • Estates Office
    Faculty phone: 
    +372 737 5137
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Finance Office
    Faculty phone: 
    +372 737 5125
    Faculty address: 
    Jakobi 4, 51005 Tartu
  • Grant Office
    Faculty phone: 
    +372 737 6215
    Faculty address: 
    Raekoja plats 9, 51004 Tartu
  • Information Technology Office
    Faculty phone: 
    +372 737 6000, IT-help: +372 737 5500
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Human Resources Office
    Faculty phone: 
    +372 737 5145
    Faculty address: 
    Ülikooli 18, rooms 302 and 304, 50090 Tartu
  • Internal Audit Office
    Faculty address: 
    Ülikooli 18-244, 51005 Tartu
  • Marketing and Communication Office
    Faculty phone: 
    +372 737 5687
    Faculty address: 
    Ülikooli 18, rooms 102, 104, 209, 210, 50090 Tartu
  • Office of Academic Affairs
    Faculty phone: 
    +372 737 5620
    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • Procurement Office
    Faculty phone: 
    +372 737 6632
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Rector's Strategy Office
    Faculty phone: 
    +372 737 5600
    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • Student Council
    Faculty address: 
    Ülikooli 18b, 51005 Tartu
  • University of Tartu Press
    Faculty phone: 
    +372 737 5945
    Faculty address: 
    W. Struve 1, 50091 Tartu
Other Units
  • University of Tartu Academic Sports Club
    Faculty phone: 
    +372 737 5371
    Faculty address: 
    Ujula 4, 51008 Tartu
  • Tartu Student Village
    Faculty phone: 
    +372 740 9959
    Faculty address: 
    Narva mnt 25, 51013 Tartu
  • Tartu Students’ Club
    Faculty phone: 
    +372 730 2400
    Faculty address: 
    Kalevi 24, 51010 Tartu
  • Tartu University Hospital
    Faculty address: 
    L. Puusepa 1a, 50406 Tartu
  • University of Tartu Foundation
    Faculty phone: 
    +372 737 5852
    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • View all other units

Contacts of UT units

Faculty of Arts and Humanities
Faculty phone: 
+372 737 5341
Faculty address: 
Jakobi 2, rooms 116–121, 51005 Tartu
  • Dean's Office
    Faculty phone: 
    + 372 737 5341
    Faculty address: 
    Jakobi 2, rooms 116–121, 51005 Tartu
  • Institute of History and Archaeology
    Faculty phone: 
    +372 737 5651
    Faculty address: 
    Jakobi 2, 51005 Tartu
  • Institute of Estonian and General Linguistics
    Faculty phone: 
    +372 737 5221
    Faculty address: 
    Jakobi 2, 51005 Tartu
  • Institute of Philosophy and Semiotics
    Faculty phone: 
    +372 737 5314
    Faculty address: 
    Jakobi 2, rooms 309–352, 51005 Tartu
  • Institute of Cultural Research
    Faculty phone: 
    (+372) 737 5223
    Faculty address: 
    Ülikooli 16, 51003 Tartu
  • School of Theology and Religious Studies
    Faculty phone: 
    +372 737 5301
    Faculty address: 
    Ülikooli 18–310, 50090 Tartu
  • College of Foreign Languages and Cultures
    Faculty address: 
    J. Liivi 4, 50409, Tartu
  • Viljandi Culture Academy
    Faculty phone: 
    +372 435 5232
    Faculty address: 
    Posti 1, 71004 Viljandi
Faculty of Social Sciences
Faculty phone: 
+372 737 5957
Faculty address: 
Lossi 36, 51003 Tartu
  • Dean's Office
    Faculty phone: 
    + 372 737 5900
    Faculty address: 
    Lossi 36, 51003 Tartu
  • Institute of Education
    Faculty phone: 
    +372 737 6440
    Faculty address: 
    Salme 1a–29, 50103 Tartu
  • Johan Skytte Institute of Political Studies
    Faculty phone: 
    +372 737 5582
    Faculty address: 
    Lossi 36–301, 51003 Tartu
  • School of Economics and Business Administration
    Faculty phone: 
    +372 737 6310
    Faculty address: 
    Narva mnt 18, 51009 Tartu
  • Institute of Psychology
    Faculty phone: 
    +372 737 5902
    Faculty address: 
    Näituse 2, 50409 Tartu
  • School of Law
    Faculty phone: 
    +372 737 5390
    Faculty address: 
    Näituse 20–324, 50409 Tartu
  • Institute of Social Studies
    Faculty phone: 
    +372 737 5188
    Faculty address: 
    Lossi 36, 51003 Tartu
  • Narva College
    Faculty phone: 
    +372 740 1900
    Faculty address: 
    Raekoja plats 2, 20307 Narva
  • Pärnu College
    Faculty phone: 
    +372 445 0520
    Faculty address: 
    Ringi 35, 80012 Pärnu
Faculty of Medicine
Faculty phone: 
+372 737 5326
Faculty address: 
Ravila 19, 50411 Tartu
  • Dean's Office
    Faculty phone: 
    +372 737 5326
    Faculty address: 
    Ravila 19, 50411 Tartu
  • Institute of Biomedicine and Translational Medicine
    Faculty phone: 
    +372 737 4210
    Faculty address: 
    Biomeedikum, Ravila 19, 50411 Tartu
  • Institute of Pharmacy
    Faculty phone: 
    +372 737 5286
    Faculty address: 
    Nooruse 1, 50411 Tartu
  • Institute of Dentistry
    Faculty phone: 
    +372 731 9856
    Faculty address: 
    Raekoja plats 6, 51003 Tartu
  • Institute of Clinical Medicine
    Faculty phone: 
    +372 737 5323
    Faculty address: 
    L. Puusepa 8, 50406 Tartu
  • Institute of Family Medicine and Public Health
    Faculty phone: 
    +372 737 4190
    Faculty address: 
    Ravila 19, 50411 Tartu
  • Institute of Sport Sciences and Physiotherapy
    Faculty phone: 
    +372 737 5360
    Faculty address: 
    Jakobi 5–205, 51005 Tartu
Faculty of Science and Technology
Faculty phone: 
+372 737 5820
Faculty address: 
Vanemuise 46–208, 51014 Tartu
  • Dean's Office
    Faculty phone: 
    +372 737 5820
    Faculty address: 
    Vanemuise 46–208, 51003 Tartu
  • Institute of Computer Science
    Faculty phone: 
    +372 737 5445
    Faculty address: 
    Narva mnt 18, 51009 Tartu
  • Estonian Marine Institute
    Faculty phone: 
    +372 671 8902
    Faculty address: 
    Mäealuse 14, 12618 Tallinn
  • Institute of Physics
    Faculty address: 
    W. Ostwaldi 1, 50411 Tartu
  • Institute of Chemistry
    Faculty phone: 
    +372 737 5261
    Faculty address: 
    Ravila 14a, 50411 Tartu
  • Institute of Mathematics and Statistics
    Faculty phone: 
    +372 737 5860
    Faculty address: 
    Narva mnt 18, 51009 Tartu
  • Institute of Molecular and Cell Biology
    Faculty phone: 
    +372 737 5027
    Faculty address: 
    Riia 23, 23b–134, 51010 Tartu
  • Tartu Observatory
    Faculty phone: 
    +372 737 4510
    Faculty address: 
    Observatooriumi 1, Tõravere, 61602 Tartumaa
  • Institute of Technology
    Faculty phone: 
    +372 737 4800
    Faculty address: 
    Nooruse 1, 50411 Tartu
  • Institute of Ecology and Earth Sciences
    Faculty phone: 
    +372 737 5835
    Faculty address: 
    Vanemuise 46, 51003 Tartu
Institutions
  • Library
    Faculty phone: 
    +372 737 5702
    Faculty address: 
    W. Struve 1, 50091 Tartu
  • Youth Academy
    Faculty phone: 
    +372 737 5581
    Faculty address: 
    Uppsala 10, 51003 Tartu
  • Institute of Genomics
    Faculty phone: 
    +372 737 4000
    Faculty address: 
    Riia 23b, 51010 Tartu
  • Museum
    Faculty phone: 
    +372 737 5674
    Faculty address: 
    Lossi 25, 51003 Tartu
  • University of Tartu Natural History Museum and Botanical Garden
    Faculty phone: 
    +372 737 6076
    Faculty address: 
    Vanemuise 46, 51003 Tartu
Support Units
  • Administrative Office
    Faculty phone: 
    +372 737 5606
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Centre for Entrepreneurship and Innovation
    Faculty phone: 
    +372 737 4809
    Faculty address: 
    Narva mnt 18, 51009, Tartu
  • University Office in Tallinn
    Faculty phone: 
    +372 737 6600
    Faculty address: 
    Teatri väljak 3, 10143 Tallinn
  • Estates Office
    Faculty phone: 
    +372 737 5137
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Finance Office
    Faculty phone: 
    +372 737 5125
    Faculty address: 
    Jakobi 4, 51005 Tartu
  • Grant Office
    Faculty phone: 
    +372 737 6215
    Faculty address: 
    Raekoja plats 9, 51004 Tartu
  • Information Technology Office
    Faculty phone: 
    +372 737 6000, IT-help: +372 737 5500
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Human Resources Office
    Faculty phone: 
    +372 737 5145
    Faculty address: 
    Ülikooli 18, rooms 302 and 304, 50090 Tartu
  • Internal Audit Office
    Faculty address: 
    Ülikooli 18-244, 51005 Tartu
  • Marketing and Communication Office
    Faculty phone: 
    +372 737 5687
    Faculty address: 
    Ülikooli 18, rooms 102, 104, 209, 210, 50090 Tartu
  • Office of Academic Affairs
    Faculty phone: 
    +372 737 5620
    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • Procurement Office
    Faculty phone: 
    +372 737 6632
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Rector's Strategy Office
    Faculty phone: 
    +372 737 5600
    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • Student Council
    Faculty address: 
    Ülikooli 18b, 51005 Tartu
  • University of Tartu Press
    Faculty phone: 
    +372 737 5945
    Faculty address: 
    W. Struve 1, 50091 Tartu
Other Units
  • University of Tartu Academic Sports Club
    Faculty phone: 
    +372 737 5371
    Faculty address: 
    Ujula 4, 51008 Tartu
  • Tartu Student Village
    Faculty phone: 
    +372 740 9959
    Faculty address: 
    Narva mnt 25, 51013 Tartu
  • Tartu Students’ Club
    Faculty phone: 
    +372 730 2400
    Faculty address: 
    Kalevi 24, 51010 Tartu
  • Tartu University Hospital
    Faculty address: 
    L. Puusepa 1a, 50406 Tartu
  • University of Tartu Foundation
    Faculty phone: 
    +372 737 5852
    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • View all other units

Reet Reinart-Okugbeni "Katsesüsteemid ligandide sidumisomaduste ja aktiivsuse alatüüp-selektiivseks iseloomustamiseks dopamiini retseptoritel"

Date: 
02.11.2012 - 10:00 to 12:00

Supervisor: Prof. Ago Rinken, MD, PhD, Keemia Instituut
Opponent: Prof. Mika Scheinin, MD, PhD, University of Turku, Finland

Summary:
"Assay systems for characterisation of subtype-selective binding and functional activity of ligands on dopamine receptors"

Dopamine has several functions in central nervous system including voluntary movement, feeding, affect, reward, sleep, attention, working memory, and learning. In the periphery, dopamine plays important physiological roles in the regulation of olfaction, retinal processes, hormonal regulation, cardiovascular functions, sympathetic regulation, immune system, and renal functions, among others. Dopaminergic ligands, substances acting on dopamine receptors, have remained an active area in the development of CNS drugs, agonists mainly in the treatment of Parkinson's disease and antagonist as antipsychotics in the treatment of schizophrenia.
Within current study the binding and function of dopamine receptors was studied in various model systems such as Sf9 insect cell line, striatal tissue of rat brain, CHO and fibroblast cell lines, and HEK293 cells.
Sf9 cells of insect origin was used a relatively "clean" cell line for studying the interaction between dopamine D1 and adenosine A1 receptors. In this cell line, A1-D1 receptor antagonistic interaction was revealed only when the cells expressed both Gi- and Gs- proteins necessary for the activity of either receptor, and on the level of cyclic AMP not on the level of agonist affinity, as previously reported. This suggests that the antagonistic interactions observed in various studies might be more complicated than previously thought.
High expression of dopamine D1 and D2 receptor expression was shown in rat striatum with proper ligand binding and G-protein coupling profiles. Nevertheless, in the level of second messenger, cAMP, the D1 receptor activation could be clearly detected, whereas the D2 receptor-mediated signalling remained hidden in [3H]cAMP assay. Therefore [3H]cAMP assay is suitable for selective discrimination of D1 receptor signalling events in rat striatal tissue.
Dopamine receptor binding of newly synthesised ligands was initially studied on D1 and D2 receptors expressed in fibroblast and CHO cell lines, respectively. The differences in cellular environment of the two expressed receptor subtypes, as well as a need to screen new ligands on all three major dopamine receptor subtypes - D1, D2L and D3 - however triggered the development of a more comparable assay system. The obtained HEK293 cell-based dopamine D1, D2L and D3 receptor stable cell lines were characterised for their binding and functional properties using subtype-selective and non-selective dopaminergic ligands. Functional properties of the receptors were studied on the level of G-protein activation (studing the effect of GTP_S binding on agonist affinity) and activation of adenylate cyclase (modulation of cyclic AMP level by agonists and antagonists). While GTP_S effectively modulated agonist binding to D1 and D2L receptor, the effect on D3 receptor binding was negligible, suggesting a weak interaction of D3 receptors and G-proteins. This was further supported by [3H]cAMP binding assay in which agonist response to D1 and D2L receptor activation was reproducibly reflected in modulation of the level of cAMP, whereas results of D3 receptor activation were contradictory. When receptor activation was measured in a dynamic cAMP mode using the BacMam Epac2-camps cAMP-biosensor we could reliably detect modulation of cAMP levels by all the three receptor subtypes, suggesting that the D3 receptor indeed was effectively coupled to its G-proteins despite the lack of GTP_S sensitivity and the lack of cAMP-response in [3H]cAMP assay.
Despite minor limitations of the developed dopamine receptor cell lines in functional assays, they were effectively used in screening of ligand binding and activity of series of new 1- and 3-substituted apomorphines and 3-azabicyclo[3.1.0]hexane derivatives in cooperation with other research groups involved in ligand synthesis.

Organizer: 
Location: 
Ravila St 14A, room 1020
Event category: