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001-es BibID:BIBFORM089428
035-os BibID:(cikkazonosító)114310 (Scopus)85097002422 (WOS)000604265300002 (PubMed)33130130
Első szerző:Kelemen Balázs (biológus)
Cím:The TRPM3 ion channel mediates nociception but not itch evoked by endogenous pruritogenic mediators / Balázs Kelemen, Silvia Pinto, Nawoo Kim, Erika Lisztes, Martin Hanyicska, Anita Vladár, Attila Oláh, Zsófia Pénzes, Brian Shu, Joris Vriens, Tamás Bíró, Tibor Rohács, Thomas Voets, Balázs István Tóth
Dátum:2021
ISSN:0006-2952
Megjegyzések:During the molecular transduction of itch, the stimulation of pruriceptors on sensory fibers leads to the activation or sensitization of ion channels, which results in a consequent depolarization of the neurons. These ion channels mostly belong to the transient receptor potential (TRP) channels, which are involved in nociception and thermosensation. In particular, TRPV1 and TRPA1 were described in the transduction of both thermal nociception as well as histaminergic and non-histaminergic itch. The thermosensitive TRPM3 plays an indispensable role in heat nociception together with TRPV1 and TRPA1. However, the role of TRPM3 in the development of pruritus has not been studied yet. Therefore, in this study we aimed at investigating the potential role of TRPM3 in the transduction of pruritus and pain by investigating itch- and nociception-related behavior of Trpm3+/+ and Trpm3?/? mice, and by studying the activation of somatosensory neurons isolated from trigeminal ganglia upon application of algogenic and pruritogenic substances. Activators of TRPM3 evoked only nocifensive responses, but not itch in Trpm3+/+ animals, and these nocifensive responses were abolished in the Trpm3?/? strain. Histamine and endogenous non-histaminergic pruritogens induced itch in both Trpm3+/+ and Trpm3?/? mice to a similar extent. Genetic deletion or pharmacological blockade diminished TRPM3 mediated Ca2+ responses of sensory neurons, but did not affect responses evoked by pruritogenic substances. Our results demonstrate that, in contrast to other thermosensitive TRP channels, TRPM3 selectively mediates nociception, but not itch sensation, and suggest that TRPM3 is a promising candidate to selectively target pain sensation.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Nociception
Itch
TRP channels
TRPM3
Cheek model
Endogenous pruritogens
Megjelenés:Biochemical Pharmacology. - 183 (2021), p. 114310. -
További szerzők:Pinto, Silvia Kim, Nawoo Lisztes Erika (1986-) (élettanász) Hanyicska Martin (1992-) (biotechnológus) Vladár Anita Oláh Attila (1984-) (élettanász) Pénzes Zsófia (1992-) (klinikai laboratóriumi kutató) Shu, Brian Vriens, Joris Bíró Tamás (1968-) (élettanász) Rohács Tibor Voets, Thomas Tóth István Balázs (1978-) (élettanász)
Pályázati támogatás:K_120187
OTKA
PD_121360
OTKA
PD-134791
OTKA
FK_125055
OTKA
GINOP-2.3.2-15-2016-00015
GINOP
EFOP-3.6.3- VEKOP-16-2017-00009
EFOP
EFOP-3.6.1-16-2016-00022
EFOP
ÚNKP-20-5-DE-422
ÚNKP
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
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2.

001-es BibID:BIBFORM083138
035-os BibID:(Scopus)85079239909 (WOS)000527342900032 (cikkazonosító)113826 (PubMed)31987857
Első szerző:Kelemen Balázs (biológus)
Cím:Volatile anaesthetics inhibit the thermosensitive nociceptor ion channel transient receptor potential melastatin 3 (TRPM3) / Balázs Kelemen, Erika Lisztes, Anita Vladár, Martin Hanyicska, János Almássy, Attila Oláh, Attila Gábor Szöllősi, Zsófia Pénzes, János Posta, Thomas Voets, Tamás Bíró, Balázs István Tóth
Dátum:2020
ISSN:0006-2952
Megjegyzések:Background Volatile anaesthetics (VAs) are the most widely used compounds to induce reversible loss of consciousness and maintain general anaesthesia during surgical interventions. Although the mechanism of their action is not yet fully understood, it is generally believed, that VAs depress central nervous system functions mainly through modulation of ion channels in the neuronal membrane, including 2-pore-domain K+ channels, GABA and NMDA receptors. Recent research also reported their action on nociceptive and thermosensitive TRP channels expressed in the peripheral nervous system, including TRPV1, TRPA1, and TRPM8. Here, we investigated the effect of VAs on TRPM3, a less characterized member of the thermosensitive TRP channels playing a central role in noxious heat sensation. Methods We investigated the effect of VAs on the activity of recombinant and native TRPM3, by monitoring changes in the intracellular Ca2+ concentration and measuring TRPM3-mediated transmembrane currents. Results All the investigated VAs (chloroform, halothane, isoflurane, sevoflurane) inhibited both the agonist-induced (pregnenolone sulfate, CIM0216) and heat-activated Ca2+ signals and transmembrane currents in a concentration dependent way in HEK293T cells overexpressing recombinant TRPM3. Among the tested VAs, halothane was the most potent blocker (IC50=0.52?0.05 mM). We also investigated the effect of VAs on native TRPM3 channels expressed in sensory neurons of the dorsal root ganglia. While VAs activated certain sensory neurons independently of TRPM3, they strongly and reversibly inhibited the agonist-induced TRPM3 activity. Conclusions These data provide a better insight into the molecular mechanism beyond the analgesic effect of VAs and propose novel strategies to attenuate TRPM3 dependent nociception.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Volatile anaesthetics
TRP ion channels
TRPM3
Nociception
Thermosensation
Megjelenés:Biochemical Pharmacology. - 174 (2020), p. 113826. -
További szerzők:Lisztes Erika (1986-) (élettanász) Vladár Anita Hanyicska Martin (1992-) (biotechnológus) Almássy János (1981-) (élettanász, biológus, angol-magyar szakfordító) Oláh Attila (1984-) (élettanász) Szöllősi Attila Gábor (1982-) (élettanász) Pénzes Zsófia (1992-) (klinikai laboratóriumi kutató) Posta János (1964-) (vegyész, toxikológus) Voets, Thomas Bíró Tamás (1968-) (élettanász) Tóth István Balázs (1978-) (élettanász)
Pályázati támogatás:GINOP-2.3.2-15-2016-00050
GINOP
ÚNKP-19-4-DE-287
Egyéb
ÚNKP-19-4-DE-142
Egyéb
ÚNKP-19-3-I-DE-140
Egyéb
ÚNKP-19-4-DE-285
Egyéb
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
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3.

001-es BibID:BIBFORM119089
Első szerző:Tóth István Balázs (élettanász)
Cím:Direct modulation of TRPM8 ion channels by rapamycin and analog macrolide immunosuppressants / Balázs István Tóth, Bahar Bazeli, Annelies Janssens, Erika Lisztes, Márk Racskó, Balázs Kelemen, Mihály Herczeg, Tamás Milán Nagy, Katalin E. Kövér, Argha Mitra, Attila Borics, Tamás Bíró, Thomas Voets
Dátum:2024
ISSN:2050-084X
Megjegyzések:Rapamycin (sirolimus), a macrolide compound isolated from the bacterium Streptomyces hygroscopicus, is widely used as oral medication for the prevention of transplant rejection and the treatment of lymphangioleiomyomatosis. It is also incorporated in coronary stent coatings to prevent restenosis and in topical preparations for the treatment of skin disorders. Rapamycin's in vivo activities are generally ascribed to its binding to the protein FKBP12, leading to potent inhibition of the mechanistic target of rapamycin kinase (mTOR) by the FKBP12-rapamycin complex. The specific rapamycin-induced interaction between domains from mTOR and FKBP12 is also frequently employed in cell biological research, for rapid chemically-induced protein dimerization strategies. Here we show that rapamycin activates TRPM8, a cation channel expressed in sensory nerve endings that serves as the primary cold sensor in mammals. Using a combination of electrophysiology, Saturation Transfer Triple-Difference (STTD) NMR spectroscopy and molecular docking-based targeted mutagenesis, we demonstrate that rapamycin directly binds to TRPM8. We identify a rapamycin-binding site in the groove between voltage sensor-like domain and the pore domain, distinct from the interaction sites of cooling agents and known TRPM8 agonists menthol and icilin. Related macrolide immunosuppressants act as partial TRPM8 agonists, competing with rapamycin for the same binding site. These findings identify a novel molecular target for rapamycin and provide new insights into the mechanisms of TRPM8 activation, which may assist in the development of therapies targeting this ion channel. Moreover, our findings also indicate that caution is needed when using molecular approaches based on rapamycin-induced dimerization to study ion channel regulation.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
TRPM8
Rapamycin
Electrophysiology
NMR spectroscopy
Neuroscience
Megjelenés:eLife. - "Accepted by Publisher" (2024). -
További szerzők:Bazeli, Bahar Janssens, Annelies Lisztes Erika (1986-) (élettanász) Racskó Márk (1991-) (molekuláris biológus) Kelemen Balázs (1992-) (biológus) Herczeg Mihály (1979-) (vegyész, biológia-kémia tanár) Nagy Tamás Milán (1993-) (vegyész, nmr) Kövér Katalin, E. (1956-2023) (vegyész) Mitra, Argha Borics Attila Bíró Tamás (1968-) (élettanász) Voets, Thomas
Pályázati támogatás:134725
OTKA
134791
OTKA
128368
OTKA
137924
OTKA
GINOP-2.3.2-15-2016-00050
GINOP
GINOP-2.3.3-15-2016-00004
GINOP
GINOP-2.2.1-15-2017-00044
GINOP
János Bolyai Research Scholarship
Egyéb
ÚNKP-22-3-I-DE-324
Egyéb
ÚNKP-23-3-II-DE-430
Egyéb
UNKP-22-4-I-DE-87
Egyéb
ÚNKP-21-5-DE-491
Egyéb
FWO; G0B9520N
Egyéb
FWO; G0B7620N
Egyéb
esearch Council of KU Leuven (C2-TRP)
Egyéb
Queen Elisabeth Medical Foundation for Neurosciences
Egyéb
EU's Horizon 2020 research and innovation program under grant agreement No. 739593
Egyéb
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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