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New insights into the effects of organometallic ruthenium complexes on nicotinic acetylcholine receptors
ID
Trobec, Tomaž
(
Avtor
),
ID
Lamassiaude, Nicolas
(
Avtor
),
ID
Benoit, Evelyne
(
Avtor
),
ID
Žužek, Monika C.
(
Avtor
),
ID
Sepčić, Kristina
(
Avtor
),
ID
Kladnik, Jerneja
(
Avtor
),
ID
Turel, Iztok
(
Avtor
),
ID
Aráoz, Rómulo
(
Avtor
),
ID
Frangež, Robert
(
Avtor
)
PDF - Predstavitvena datoteka,
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(3,26 MB)
MD5: 72BC7414B278054029AE8BFB2C5F62FF
URL - Izvorni URL, za dostop obiščite
https://www.sciencedirect.com/science/article/pii/S0009279724003594
Galerija slik
Izvleček
Nicotinic acetylcholine receptors (nAChRs) are expressed in excitable and non-excitable cells of the organism. Extensive studies suggest that nAChR ligands have therapeutic potential, notably for neurological and psychiatric disorders. Organometallic ruthenium complexes are known to inhibit several medically important enzymes such as cholinesterases. In addition, they can also interact with muscle- and neuronal-subtype nAChRs. The present study aimed to investigate the direct effects of three organometallic ruthenium complexes, [(η$^6$-p-cymene)Ru(II)(5-nitro-1,10-phenanthroline)Cl]Cl (C1–Cl), [(η$^6$-p-cymene)Ru(II)(1-hydroxypyridine-2(1H)-thionato)Cl] (C1a) and [(η$^6$-p-cymene)Ru(II)(1-hydroxy-3-methoxypyridine-2(1H)-thionato)pta]PF$_6$ (C1), on muscle-subtype (Torpedo) nAChRs and on the two most abundant human neuronal-subtype nAChRs in the CNS (α4β2 and α7) expressed in Xenopus laevis oocytes, using the two-electrode voltage-clamp. The results show that none of the three compounds had agonistic activity on any of the nAChR subtypes studied. In contrast, C1–Cl reversibly blocked Torpedo nAChR (half-reduction of ACh-evoked peak current amplitude by 332 nM of compound). When tested at 10 μM, C1–Cl was statistically more potent to inhibit TorpedonAChR than α4β2 and α7 nAChRs. Similar results of C1 effects were obtained on Torpedo and α4β2 nAChRs, while no action of the compound was detected on α7 nAChRs. Finally, the effects of C1a were statistically similar on the three nAChR subtypes but, in contrast to C1–Cl and C1, the inhibition was hardly reversible. These results, together with our previous studies on isolated mouse neuromuscular preparations, strongly suggest that C1–Cl is, among the three compounds studied, the only molecule that could be used as a potential myorelaxant drug.
Jezik:
Angleški jezik
Ključne besede:
organometallic ruthenium complexes
,
nicotinic acetylcholine receptors
,
nicotinic antagonists
,
electrophysiology
,
two-electrode voltage-clamp technique
Vrsta gradiva:
Članek v reviji
Tipologija:
1.01 - Izvirni znanstveni članek
Organizacija:
VF - Veterinarska fakulteta
BF - Biotehniška fakulteta
FKKT - Fakulteta za kemijo in kemijsko tehnologijo
Status publikacije:
Objavljeno
Različica publikacije:
Objavljena publikacija
Leto izida:
2024
Št. strani:
7 str.
Številčenje:
Vol. 402, art. 111213
PID:
20.500.12556/RUL-160689
UDK:
616-092
ISSN pri članku:
1872-7786
DOI:
10.1016/j.cbi.2024.111213
COBISS.SI-ID:
205689347
Datum objave v RUL:
03.09.2024
Število ogledov:
241
Število prenosov:
55
Metapodatki:
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Objavi na:
Gradivo je del revije
Naslov:
Chemico-biological interactions
Založnik:
Elsevier
ISSN:
1872-7786
COBISS.SI-ID:
23211013
Licence
Licenca:
CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:
http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:
To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
Projekti
Financer:
ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:
P4-0053
Naslov:
Endokrini, imunski in encimski odzivi pri zdravih in bolnih živalih
Financer:
ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:
P1-0207
Naslov:
Toksini in biomembrane
Financer:
ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:
P1-0175
Naslov:
Napredna anorganska kemija
Financer:
ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:
BI-FR/21-22-PROTEUS-002
Akronim:
PROTEUS
Financer:
ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Program financ.:
Young researchers
Financer:
Drugi - Drug financer ali več financerjev
Program financ.:
French Alternative Energies and Atomic Energy Commission (CEA)
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