TY  - JOUR
AU  - Mijušković, Ana
AU  - Nikolić-Kokić, Aleksandra
AU  - Oreščanin-Dušić, Zorana
AU  - Slavić, Marija
AU  - Spasić, Mihajlo
AU  - Blagojević, Duško
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1934
AB  - Background and PurposeHydrogen sulphide reduces uterine contractility
   and is of potential interest as a treatment for uterine disorders. The
   aim of this study was to explore the mechanism of sodium sulphide
   (Na2S)-induced relaxation of rat uterus, investigate the importance of
   redox effects and ion channel-mediated mechanisms, and any interactions
   between these two mechanisms.
   Experimental ApproachOrgan bath studies were employed to assess the
   pharmacological effects of Na2S in uterine strips by exposing them to
   Na2S with or without Cl- channel blockers (DIDS, NFA, IAA-94,
   T16Ainh-A01, TA), raised KCl (15 and 75mM), K+ channel inhibitors
   (glibenclamide, TEA, 4-AP), L-type Ca2+ channel activator (S-Bay K
   8644), propranolol and methylene blue. The activities of antioxidant
   enzymes were measured in homogenates of treated uteri. The expression of
   bestrophin channel 1 (BEST-1) was determined by Western blotting and
   RT-PCR.
   Key ResultsNa(2)S caused concentration-dependent reversible relaxation
   of spontaneously active and calcium-treated uteri, affecting both
   amplitude and frequency of contractions. Uteri exposed to 75mM KCl were
   less sensitive to Na2S compared with uteri in 15mM KCl. Na2S-induced
   relaxations were abolished by DIDS, but unaffected by other modulators
   or by the absence of extracellular HCO3-, suggesting the involvement of
   chloride ion channels. Na2S in combination with different modulators
   provoked specific changes in the anti-oxidant profiles of uteri. The
   expression of BEST-1, both mRNA and protein, was demonstrated in rat
   uteri.
   Conclusions and ImplicationsThe relaxant effects of Na2S in rat uteri
   are mediated mainly via a DIDS-sensitive Cl--pathway. Components of the
   relaxation are redox- and Ca2+-dependent.
T2  - British Journal of Pharmacology
T1  - Chloride channels mediate sodium sulphide-induced relaxation in rat
 uteri
IS  - 14, SI
VL  - 172
DO  - 10.1111/bph.13161
SP  - 3671
EP  - 3686
ER  - 

@article{
author = "Mijušković, Ana and Nikolić-Kokić, Aleksandra and Oreščanin-Dušić, Zorana and Slavić, Marija and Spasić, Mihajlo and Blagojević, Duško",
year = "2015",
abstract = "Background and PurposeHydrogen sulphide reduces uterine contractility
   and is of potential interest as a treatment for uterine disorders. The
   aim of this study was to explore the mechanism of sodium sulphide
   (Na2S)-induced relaxation of rat uterus, investigate the importance of
   redox effects and ion channel-mediated mechanisms, and any interactions
   between these two mechanisms.
   Experimental ApproachOrgan bath studies were employed to assess the
   pharmacological effects of Na2S in uterine strips by exposing them to
   Na2S with or without Cl- channel blockers (DIDS, NFA, IAA-94,
   T16Ainh-A01, TA), raised KCl (15 and 75mM), K+ channel inhibitors
   (glibenclamide, TEA, 4-AP), L-type Ca2+ channel activator (S-Bay K
   8644), propranolol and methylene blue. The activities of antioxidant
   enzymes were measured in homogenates of treated uteri. The expression of
   bestrophin channel 1 (BEST-1) was determined by Western blotting and
   RT-PCR.
   Key ResultsNa(2)S caused concentration-dependent reversible relaxation
   of spontaneously active and calcium-treated uteri, affecting both
   amplitude and frequency of contractions. Uteri exposed to 75mM KCl were
   less sensitive to Na2S compared with uteri in 15mM KCl. Na2S-induced
   relaxations were abolished by DIDS, but unaffected by other modulators
   or by the absence of extracellular HCO3-, suggesting the involvement of
   chloride ion channels. Na2S in combination with different modulators
   provoked specific changes in the anti-oxidant profiles of uteri. The
   expression of BEST-1, both mRNA and protein, was demonstrated in rat
   uteri.
   Conclusions and ImplicationsThe relaxant effects of Na2S in rat uteri
   are mediated mainly via a DIDS-sensitive Cl--pathway. Components of the
   relaxation are redox- and Ca2+-dependent.",
journal = "British Journal of Pharmacology",
title = "Chloride channels mediate sodium sulphide-induced relaxation in rat
 uteri",
number = "14, SI",
volume = "172",
doi = "10.1111/bph.13161",
pages = "3671-3686"
}

Mijušković, A., Nikolić-Kokić, A., Oreščanin-Dušić, Z., Slavić, M., Spasić, M.,& Blagojević, D.. (2015). Chloride channels mediate sodium sulphide-induced relaxation in rat
 uteri. in British Journal of Pharmacology, 172(14, SI), 3671-3686.
https://doi.org/10.1111/bph.13161

Mijušković A, Nikolić-Kokić A, Oreščanin-Dušić Z, Slavić M, Spasić M, Blagojević D. Chloride channels mediate sodium sulphide-induced relaxation in rat
 uteri. in British Journal of Pharmacology. 2015;172(14, SI):3671-3686.
doi:10.1111/bph.13161 .

Mijušković, Ana, Nikolić-Kokić, Aleksandra, Oreščanin-Dušić, Zorana, Slavić, Marija, Spasić, Mihajlo, Blagojević, Duško, "Chloride channels mediate sodium sulphide-induced relaxation in rat
 uteri" in British Journal of Pharmacology, 172, no. 14, SI (2015):3671-3686,
https://doi.org/10.1111/bph.13161 . .

TY  - JOUR
AU  - Mijušković, Ana
AU  - Spasić, Mihajlo
PY  - 2012
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/399
AB  - Two American scientists Robert J. Lefkowitz and Brian K. Kobilka won the 2012 Nobel Prize in Chemistry. They were awarded 'for groundbreaking discoveries that reveal the inner workings of an important family of such receptors: G-protein-coupled receptors', said the academy in a statement, adding that the studies by Lefkowitz and Kobilka are crucial for understanding how G-protein-coupled receptors function. Fine-tuned communication between individual cells is a prerequisite for maintaining homeostasis within a living organism. Cells have the ability to process amounts of information conveyed to them by extracellular About a thousand genes code for such receptors, for example, for light, flavor, odor, adrenalin, dopamine and serotonin and about half of all medications achieve their effect through GPCRs. Unfortunately for a long time, it wasn’t possible to study the detailed structure of GPCRs because of the great difficulties in crystallizing them. This Nobel Prize continues the proud tradition of recognizing crystallographers who are among the most persistent and fearless of all scientists.
AB  - Najvažnije, kao i u svim drugim velikim otkrićima, rad Kobilke i Lefkovica postavio je mnogo pitanja što ukazuje na uzbudljive, neistražene teritorije. Najznačajnije otkriće u ovom kontekstu je da dva slična molekula - dva agonista - mogu aktivirati proteine na drugačiji način, dovodeći do potpuno različitih fizioloških odgovora, takozvanog fenomena: 'funkcionalna selektivnost'. Ovo proističe iz diferencijalne interakcije GPCR sa G proteinima, arestinima i drugim proteinima u ćeliji. Izuzetno, funkcionalna selektivnost može dovesti do istog molekulskog događaja, zavisno od fiziološkog odgovora koji je posredovan proteinima. Zato je funkcionisanje GPCR poput Bahove simfonije Prirode, više set nezavisnih nota gde kombinacija interakcija radije nego vezivanje pojedinačnog odgovora rezultuje kompleksnim fiziološkim odgovorom. Rad ovogodišnjih Nobelovaca, otvorio je vrata razumevanju kako se ova simfonija sprovodi. U istoriji dodeljivanja Nobelove nagrade do sada su zabeleženi brojni slučajevi da su Nobelovu nagradu za medicinu dobili hemičari, ovo je po našem saznanju prvi put da su lekari dobili Nobelovu nagradu za hemiju. Struktura elemenata regulacije metabolizma i spoznaja njihove funkcije da bi se uskladio životni ciklus organizma sa promenama u spoljnoj sredini su ishodište hemije, važan cilj biohemije i uvod u dalji razvoj primenjenih discipline kao što su medicina, veterina, poljoprivreda i farmacija. U ovom slučaju značaj različitih efekata koje adrenalin ima u tkivima inicirao je interes lekara za strukturu posrednika u prenosu signala. To su uspešno rešili primenomklasičnih hemijskih i biohemiskih metoda (kristalografija) i u sprezi sa rezultatima molekularne biologije (humani genom) što potvrđuje neophodnost interdisciplinarnih istraživanja.
T2  - Hemijski pregled
T1  - Receptori spregnuti sa G proteinima - Nobelova nagrada za Hemiju 2012.
T1  - The Nobel Prize in Chemistry 2012 for studies of G-protein coupled receptors
IS  - 6
VL  - 53
SP  - 142
EP  - 147
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_399
ER  - 

@article{
author = "Mijušković, Ana and Spasić, Mihajlo",
year = "2012, 2012",
abstract = "Two American scientists Robert J. Lefkowitz and Brian K. Kobilka won the 2012 Nobel Prize in Chemistry. They were awarded 'for groundbreaking discoveries that reveal the inner workings of an important family of such receptors: G-protein-coupled receptors', said the academy in a statement, adding that the studies by Lefkowitz and Kobilka are crucial for understanding how G-protein-coupled receptors function. Fine-tuned communication between individual cells is a prerequisite for maintaining homeostasis within a living organism. Cells have the ability to process amounts of information conveyed to them by extracellular About a thousand genes code for such receptors, for example, for light, flavor, odor, adrenalin, dopamine and serotonin and about half of all medications achieve their effect through GPCRs. Unfortunately for a long time, it wasn’t possible to study the detailed structure of GPCRs because of the great difficulties in crystallizing them. This Nobel Prize continues the proud tradition of recognizing crystallographers who are among the most persistent and fearless of all scientists., Najvažnije, kao i u svim drugim velikim otkrićima, rad Kobilke i Lefkovica postavio je mnogo pitanja što ukazuje na uzbudljive, neistražene teritorije. Najznačajnije otkriće u ovom kontekstu je da dva slična molekula - dva agonista - mogu aktivirati proteine na drugačiji način, dovodeći do potpuno različitih fizioloških odgovora, takozvanog fenomena: 'funkcionalna selektivnost'. Ovo proističe iz diferencijalne interakcije GPCR sa G proteinima, arestinima i drugim proteinima u ćeliji. Izuzetno, funkcionalna selektivnost može dovesti do istog molekulskog događaja, zavisno od fiziološkog odgovora koji je posredovan proteinima. Zato je funkcionisanje GPCR poput Bahove simfonije Prirode, više set nezavisnih nota gde kombinacija interakcija radije nego vezivanje pojedinačnog odgovora rezultuje kompleksnim fiziološkim odgovorom. Rad ovogodišnjih Nobelovaca, otvorio je vrata razumevanju kako se ova simfonija sprovodi. U istoriji dodeljivanja Nobelove nagrade do sada su zabeleženi brojni slučajevi da su Nobelovu nagradu za medicinu dobili hemičari, ovo je po našem saznanju prvi put da su lekari dobili Nobelovu nagradu za hemiju. Struktura elemenata regulacije metabolizma i spoznaja njihove funkcije da bi se uskladio životni ciklus organizma sa promenama u spoljnoj sredini su ishodište hemije, važan cilj biohemije i uvod u dalji razvoj primenjenih discipline kao što su medicina, veterina, poljoprivreda i farmacija. U ovom slučaju značaj različitih efekata koje adrenalin ima u tkivima inicirao je interes lekara za strukturu posrednika u prenosu signala. To su uspešno rešili primenomklasičnih hemijskih i biohemiskih metoda (kristalografija) i u sprezi sa rezultatima molekularne biologije (humani genom) što potvrđuje neophodnost interdisciplinarnih istraživanja.",
journal = "Hemijski pregled",
title = "Receptori spregnuti sa G proteinima - Nobelova nagrada za Hemiju 2012., The Nobel Prize in Chemistry 2012 for studies of G-protein coupled receptors",
number = "6",
volume = "53",
pages = "142-147",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_399"
}

Mijušković, A.,& Spasić, M.. (2012). Receptori spregnuti sa G proteinima - Nobelova nagrada za Hemiju 2012.. in Hemijski pregled, 53(6), 142-147.
https://hdl.handle.net/21.15107/rcub_ibiss_399

Mijušković A, Spasić M. Receptori spregnuti sa G proteinima - Nobelova nagrada za Hemiju 2012.. in Hemijski pregled. 2012;53(6):142-147.
https://hdl.handle.net/21.15107/rcub_ibiss_399 .

Mijušković, Ana, Spasić, Mihajlo, "Receptori spregnuti sa G proteinima - Nobelova nagrada za Hemiju 2012." in Hemijski pregled, 53, no. 6 (2012):142-147,
https://hdl.handle.net/21.15107/rcub_ibiss_399 .