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C60 fullerenes disrupt cellular signalling leading to TRPC4 and TRPC6 channels opening by the activation of muscarinic receptors and G-proteins in small intestinal smooth muscles.
Dryn, Dariia O; Melnyk, Mariia I; Al Kury, Lina T; Prylutskyy, Yuriy I; Ritter, Uwe; Zholos, Alexander V.
Afiliación
  • Dryn DO; A.A. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, 4 Bogomoletz Street, 01024 Kyiv, Ukraine; Institute of Pharmacology and Toxicology, National Academy of Medical Science, 14 Eugene Pottier Street, 03057 Kyiv, Ukraine.
  • Melnyk MI; A.A. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, 4 Bogomoletz Street, 01024 Kyiv, Ukraine; Institute of Pharmacology and Toxicology, National Academy of Medical Science, 14 Eugene Pottier Street, 03057 Kyiv, Ukraine.
  • Al Kury LT; Zayed University, P.O. Box 144534, Abu Dhabi, United Arab Emirates.
  • Prylutskyy YI; Taras Shevchenko National University of Kyiv, ESC "Institute of Biology and Medicine", 64 Volodymyrska Street, 01601 Kyiv, Ukraine.
  • Ritter U; Technical University of Ilmenau, Institute of Chemistry and Biotechnology, 25 Weimarer Street, 98693 Ilmenau, Germany.
  • Zholos AV; A.A. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, 4 Bogomoletz Street, 01024 Kyiv, Ukraine; Taras Shevchenko National University of Kyiv, ESC "Institute of Biology and Medicine", 64 Volodymyrska Street, 01601 Kyiv, Ukraine. Electronic address: a.zholos@univ.net.ua.
Cell Signal ; 43: 40-46, 2018 03.
Article en En | MEDLINE | ID: mdl-29242169
The effect of water-soluble pristine C60 fullerene nanoparticles (C60NPs) on receptor-operated cation channels formed by TRPC4/C6 proteins in ileal smooth muscle cells was investigated for the first time. Activation of these channels subsequent to acetylcholine binding to the expressed in these cells M2 and M3 muscarinic receptors represents the key event in the parasympathetic control of gastrointestinal smooth muscle motility and cholinergic excitation-contraction coupling. Experiments were performed on single collagenase-dispersed mouse ileal myocytes using patch-clamp techniques with symmetrical 125mM Cs+ solutions and [Ca2+]i 'clamped' at 100nM in order to isolate the muscarinic cation current (mICAT). The current was induced by intracellular infusion of 200µM GTPγS, which activates G-proteins directly, i.e. bypassing the muscarinic receptors. C60NPs applied at 10-6M at peak response to activation of G-proteins caused mICAT inhibition by 47.0±3.5% (n=9). The inhibition developed rather slowly, with the time constant of 119±16s, was voltage-independent and irreversible. Thus, C60NPs are unlikely to cause any direct block of TRPC4/C6 channels; rather, they may accumulate in the membrane and disrupt G-protein signalling leading to mICAT generation. C60NPs may represent a novel class of biocompatible molecules for the treatment of disorders associated with enhanced gastrointestinal motility.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Receptores Muscarínicos / Proteínas de Unión al GTP / Miocitos del Músculo Liso / Fulerenos / Canales Catiónicos TRPC / Canal Catiónico TRPC6 / Intestino Delgado Límite: Animals Idioma: En Revista: Cell Signal Año: 2018 Tipo del documento: Article País de afiliación: Ucrania Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Receptores Muscarínicos / Proteínas de Unión al GTP / Miocitos del Músculo Liso / Fulerenos / Canales Catiónicos TRPC / Canal Catiónico TRPC6 / Intestino Delgado Límite: Animals Idioma: En Revista: Cell Signal Año: 2018 Tipo del documento: Article País de afiliación: Ucrania Pais de publicación: Reino Unido